이 연구는 신경 장애 및 뇌졸중 (MPB)을위한 국립 연구소의 R01 NS067417에 의해 뒷받침되었다.

이 연구는 국립 연구소 건강의 실험실 동물의 관리와 사용에 대한 가이드의 권장 사항을 엄격하게 준수하여 수행되었습니다. 이 의정서는 조지 타운 대학교 (Georgetown University)의 기관 동물 관리 및 사용위원회의 승인을 받았습니다. 생쥐를 온도 조절 동물 시설에 넣고 12 시간의 빛 / 12 시간의 암주기에 두었다. 음식과 물은 자유롭게 사용할 수있었습니다. 1. mTBI 장치의 준비 참고 : mTBI 장치에는 충돌 매개 변수를 제어하는 ​​데이터 수집 (DAQ) 상자, 충격을 수행하는 고속 공기압 임팩터 및 충돌 후 헤드를 감속시키기위한 성형 젤 충진베이스가 있습니다. <ol><li> 압축 공기를 켜고 고속 공기압 임팩 터를 861.85 kPa의 압력 설정으로 초기화하십시오. </li><li> DAQ 컨트롤 시스템을 피스톤 속도 2.35 m / s, 표면 드웰 시간e는 31.5ms이다. </li><li> 정중선이 임팩터 팁의 궤적과 수직이되도록 성형 된 겔 충전베이스 (압축률 64 kPa / mm)를 놓습니다. </li></ol> 2. mTBI 충격 <ol><li> 사용할 모든 마우스의 무게를 기록하십시오. </li><li> 유도 챔버에서 120 초 동안 3 % isoflurane 산소로 마우스를 마취. </li><li> 마우스를 mTBI 장치로 옮기고 유연하고 고정되지 않은 코 콘을 통해 마취를 계속합니다. </li><li> 노우즈 콘에서 마우스 헤드를 젤 패드 위에 올려 놓으면 두개골의 평평한 표면이 임팩터 팁에 수직으로 표시됩니다. </li><li> 마우스 헤드 위로 테이프를 올려 평평한 표면을 만들고 귀를 충격 부위에서 멀리 떨어 뜨립니다. </li><li> 폴리 테트라 플루오르 에틸렌 임팩터 팁을 머리 중심의 시상 정중선과 정렬하도록 낮추십시오. 사용 된 임팩터 팁은 직경 10mm이며 눈 바로 뒤부터 귀의 정중선까지 두피 영역을 덮을 것입니다. 임팩터를 조정하여 주무세요.st는 마우스 머리의 표면을 만지고. </li><li> 임팩터 팁을 후퇴시키고 필요한 굴곡 깊이 (7.5 mm)를 수동으로 내려줍니다. </li><li> DAQ 컨트롤 시스템을 가동하고 트리거 버튼을 눌러 마우스 헤드에 영향을줍니다 (단수 또는 반복적 인 영향). 반복되는 영향은 각 충격 사이에 지체없이 연속적으로 전달됩니다. </li><li> 최종 충격 직후 마취와 mTBI 장치에서 마우스를 제거하고 앙와위 자세로 놓습니다. </li><li> 스톱워치를 사용하면 우회전 (잠복기부터 취침까지)의 복귀 대기 시간을 측정하고 의식 시간의 손실뿐 아니라 보행 시간 (방해받지 않는 걷기)을 결정할 수 있습니다. </li><li> 마우스를 모니터하고 정상적인 동작으로 회복되면 홈 케이지로 돌아갑니다. </li><li> 가짜 쥐는 동일한 취급 및 마취를 받지만 아무런 영향을받지 않습니다. </li></ol>

<ol>
	<li>McMahon, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Symptomatology+and+functional+outcome+in+mild+traumatic+brain+injury:+results+from+the+prospective+TRACK-TBI+study.">Symptomatology and functional outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study.</a> J Neurotrauma. 31 (1), 26-33 (2014).</li><li>Barkhoudarian, G., Hovda, D. A., Giza, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+pathophysiology+of+concussive+brain+injury.">The molecular pathophysiology of concussive brain injury.</a> Clin Sports Med. 30 (1), 33-48 (2011).</li><li>Blennow, K., Hardy, J., Zetterberg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuropathology+and+neurobiology+of+traumatic+brain+injury.">The neuropathology and neurobiology of traumatic brain injury.</a> Neuron. 76 (5), 886-899 (2012).</li><li>Levin, H. S., Diaz-Arrastia, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis,+prognosis,+and+clinical+management+of+mild+traumatic+brain+injury.">Diagnosis, prognosis, and clinical management of mild traumatic brain injury.</a> Lancet Neurol. 14 (5), 506-517 (2015).</li><li>McCrory, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consensus+statement+on+concussion+in+sport:+the+4th+International+Conference+on+Concussion+in+Sport,+Zurich,+November+2012.">Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport, Zurich, November 2012.</a> J Athl Train. 48 (4), 554-575 (2012).</li><li>Talavage, T. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functionally-detected+cognitive+impairment+in+high+school+football+players+without+clinically-diagnosed+concussion.">Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion.</a> J Neurotrauma. 31 (4), 327-338 (2014).</li><li>Angoa-Perez, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+sports-related+head+injury:+bridging+the+gap+between+pre-clinical+research+and+clinical+reality.">Animal models of sports-related head injury: bridging the gap between pre-clinical research and clinical reality.</a> J Neurochem. 129 (6), 916-931 (2014).</li><li>Creed, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concussive+brain+trauma+in+the+mouse+results+in+acute+cognitive+deficits+and+sustained+impairment+of+axonal+function.">Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function.</a> J Neurotrauma. 28 (4), 547-563 (2011).</li><li>Hamberger, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concussion+in+professional+football:+morphology+of+brain+injuries+in+the+NFL+concussion+model--part+16.">Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.</a> Neurosurgery. 64 (6), 1174-1182 (2009).</li><li>Kane, M. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+of+human+repetitive+mild+traumatic+brain+injury.">A mouse model of human repetitive mild traumatic brain injury.</a> J Neurosci Methods. 203 (1), 41-49 (2012).</li><li>Prins, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeat+traumatic+brain+injury+in+the+juvenile+rat+is+associated+with+increased+axonal+injury+and+cognitive+impairments.">Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments.</a> Dev Neurosci. 32 (5-6), 510-518 (2010).</li><li>Tang, Y. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+concussive-like+brain+injury+model+in+mice+(II):+selective+neuronal+loss+in+the+cortex+and+hippocampus.">A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.</a> J Neurotrauma. 14 (11), 863-873 (1997).</li><li>Winston, C. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dendritic+Spine+Loss+and+Chronic+White+Matter+Inflammation+in+a+Mouse+Model+of+Highly+Repetitive+Head+Trauma.">Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.</a> Am J Pathol. 186 (3), 552-567 (2016).</li><li>Johnson, V. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inflammation+and+white+matter+degeneration+persist+for+years+after+a+single+traumatic+brain+injury.">Inflammation and white matter degeneration persist for years after a single traumatic brain injury.</a> Brain. 136, 28-42 (2013).</li><li>Barrio, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+characterization+of+chronic+traumatic+encephalopathy+using+[F-18]FDDNP+PET+brain+imaging.">In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.</a> Proc Natl Acad Sci U S A. 112 (16), 2039-2047 (2015).</li></ol>

저자는 공개 할 것이 없습니다.

사람의 경우, mTBI는 구조적 상해가없는 경우 기능 장애를 특징으로합니다. 이것은 의식 상실을 동반하거나 동반하지 않고 발생할 수 있습니다 1 . 반복 뇌진탕에 대한 노출은 현재 CTE 4 와 같은 신경 퇴행성 질환의 발달 및 / 또는 진행의 기초가되는 것으로 생각됩니다. CTE가 사각 팬 및 축구 선수에서 흔히 발견되며 CTE를 개발하는 데 반복적 인 뇌진탕 (의식 상?...

외상성 뇌 손상 (Traumatic Brain Injury, TBI)은 외부의 물리적 인 힘으로부터 지속되는 두부 손상으로 정의되어 정상적인 뇌 기능을 손상시킵니다. 질병 통제 예방 센터 (CDC)는 매년 20 백만명의 미국인이 매년 TBI를지지한다고 추산하는 의회보고를 통해 심각한 사회 경제적 및 공중 보건 부담을 나타냅니다. 이것은 환자의 삶의 질에 영향을 줄뿐만 아니라, 현재 연간 765 억 달러로 추정되는 지역 사회에 매우 높은 경제적 비용을 부과합니다. 전달되는 실제 뇌 손상의 양과 급성기의 증상은 경증, 중등도 및 중증의 TBI를 정의합니다. 뇌진탕이라고도하는 경미한 외상성 뇌 손상 (mTBI)은 매년보고되는 TBI의 70 % 이상을 차지합니다 1 . 권투 및 축구 2를 포함하여 위험도가 높은 접촉 스포츠에 참여하는 선수들 사이에서 가장 일반적입니다. 온건파와 달리또는 심한 형태의 TBI로 인해 mTBI와 관련된 즉각적인 손상 및 증상이 때로는 분명하지 않습니다 3 . 대조적으로, mTBI의 장기적인 효과는 중등도 및 중증 형태에서 나타나는 것과 마찬가지로 쇠약해질 수 있습니다. 반복되는 mTBI로 고통받는 사람들은 만성 외상성 뇌 질환 (CTE)뿐만 아니라 기타인지 및 퇴행성 질환을 발병하는 것으로 나타났습니다 4 . 따라서 mTBI 이후에 발생하는 단기 증상 및 전반적인 장기 손상에 기여하는 메커니즘에 대한 이해를 높이는 것이 중요합니다. 사람의 경우, 스포츠 제동에 대한 제 4 차 국제 회의 (취리히 2012) 5 에 정의 된 뇌진탕의 정의는 스포츠 뇌진탕의 경미한 수준은 경미하고, 병리학 적으로 큰 변화를 일으키지 않지만 단기간의 신경 학적 결손을 유발한다고 명시합니다 자발적으로 해결됩니다. 실제로, 수신기nt 연구는 머리 충돌 원격 측정 시스템을 사용하는 고등학교 축구 선수의인지 장애에 대한 mTBI의 영향을 조사했습니다. 이 연구는 선수가 한 시즌에 20 그램을 초과하는 헬멧 충격을 견뎌내는 시간이 226 (평균, 세션 당 4.7)에서 1855 (최고, 세션 당 평균 38.6)의 최고치까지 다양하다는 것을 보여주었습니다. 이러한 충격의 대부분은 뇌진탕의 임상 진단을 초래하지는 않았다. 뇌 기능의 기능적 변화에 대한 증거는 fMRI 6을 사용하여 관찰 할 수있다. 이러한 기능적 변화를 일으키는 뇌의 변화는 알려지지 않았기 때문에, 진탕 및 협착 성 mTBI의 효과에 대한 연구를 용이하게하기 위해서는 신뢰할 수 있고 재현 가능한 모델을 필요로합니다. 생쥐와 쥐에서 mTBI를 모델링하려는 이전의 시도에도 불구하고 많은 사람들이 부작용을보고합니다. 특히, 대부분의 설치류 모델은 더 적은 th를 사용하여 반복성이 제한적입니다5 개의 mTBI는 뇌내 출혈, 두개골 골절, 심한 축삭 손상, 신경 세포 사멸, 사망률 증가 등의 이상 병리학 적 증상을 나타냅니다 8 , 9 , 10 , 11 , 12 . 여기서 우리는 인간에서 뇌진탕의 진정한 정의에 더 가까운 mTBI의 마우스 모델을 설명합니다. 이 모델은 명백한 뇌의 병리가없는 의식의 일시적인 손실을 초래하는 기계적 힘과 같은 인간 mTBI에서 관찰되는 많은 증상을 반복합니다. 더욱이 이전에보고 된 것처럼 오랜 기간 동안 단일 충격 및 반복 충격 패러다임 모두에 활용할 수 있다는 점에서 유리하다.

<table border="0" cellpadding="0" cellspacing="0" width="811">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">Powerlab 8SP data acquisition (DAQ) control box&#160;</td>
			<td style="width:203px;">(AD instruments)</td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">VIP 3000 calibrated vaporizer</td>
			<td style="width:203px;">Matrx</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isoflurane</td>
			<td style="width:203px;">Henry Schein Animal Health</td>
			<td style="width:119px;">29405</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">Oxygen</td>
			<td style="width:203px;"></td>
			<td style="width:119px;"></td>
			<td>Commercially available</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">Compressed Air</td>
			<td style="width:203px;"></td>
			<td style="width:119px;"></td>
			<td>Commercially available</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Masking Tape</td>
			<td style="width:203px;"></td>
			<td style="width:119px;"></td>
			<td>Commercially available</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stop Watch</td>
			<td style="width:203px;">Fisher Scientific</td>
			<td>02-261-840</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">C57 Bl/6 Mice</td>
			<td style="width:203px;">Jackson Laboratories</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">Digital Scale and weigh container</td>
			<td style="width:203px;">Fisher Scientific</td>
			<td>20031</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">anti-Iba1 antibody</td>
			<td style="width:203px;">Wako</td>
			<td style="width:119px;">019-19741</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:323px;">HRP labelled secondary&#160;</td>
			<td style="width:203px;">Jackson Immunoresearch</td>
			<td style="width:119px;">111-035-003</td>
			<td></td>
		</tr>
	</tbody>
</table>

a mouse model of single and repetitive mild traumatic brain injury

경미한 외상성 뇌 손상 (mTBI)은 혼란의시기, 의식 상실 (LOC), 국소 신경 학적 결손 및 기억 상실을 포함하여 뇌 기능의 급격한 상실을 초래할 수 있습니다. 접촉 스포츠에 참여하는 선수는 많은 수의 mTBI에 노출 될 위험이 높습니다. 운동 선수의 부상 정도를 보면 mTBI는 전반적인 병리학 적 변화를 일으키지 않는 경미한 부상으로 정의되지만 자발적으로 해결되는 단기간의 신경 학적 결손을 유발합니다. 마우스 및 쥐에서 mTBI를 모델링하려는 이전의 시도에도 불구하고 많은 사람들이 두개골 골절, 뇌내 출혈, 축삭 손상 및 신경 세포 죽음을 포함하는 심한 부작용을보고했다. 여기서 우리는 임상 적으로 관련된 증상을 재생하는 mTBI의 매우 재현 가능한 동물 모델을 설명합니다. 이 모델은 맞춤형 공압 임팩터 장치를 사용하여 폐두 외상을 제공합니다. 이 충격은 정밀한 속도 및 변형 파라미터 하에서 이루어지며,단일 또는 반복 진탕 mTBI의 효과에 기여하는 메커니즘을 조사 할 수있는 신뢰할 수 있고 재현 가능한 모델을 만듭니다.

이 새로운 mTBI 장치를 사용하면 두개골 골절이나 구조적 뇌 손상의 위험없이 단발적이고 반복적 인 경미한 머리 부상이 가능합니다. 이 모델은 맞춤형 공압식 Teflon 임팩터 장치를 사용하여 닫힌 머리의 기계적 에너지 충격을 전달합니다. 충격은 단일 속도 또는 반복적 인 진탕 mTBI ( 그림 1 )의 효과에 기여하는 메커니즘을 조사 할 수있는 신뢰할 수 ?...

Watch this Scientific Journal Video about A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury at JoVE.com

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

운동 선수는 매년 수백 건의 경증 외상성 뇌 손상 (mTBI) / 뇌진탕을 흡수합니다. 그러나 뇌에 대한 이들의 결과는 제대로 이해되지 못했습니다. 따라서 임상 적으로 적절한 증상을 반복적으로 반복하는 단일 및 반복 mTBI의 동물 모델은 mTBI 및 뇌진탕의 연구를 발전시킬 수있는 수단을 제공합니다.

단일 및 반복적 인 경미한 외상성 뇌 손상의 마우스 모델

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal ...

a-mouse-model-of-single-and-repetitive-mild-traumatic-brain-injury

Research

JoVE Journal

Medicine

11.0K 조회수.  Georgetown University Medical Center.  운동 선수는 매년 수백 건의 경증 외상성 뇌 손상 (mTBI) / 뇌진탕을 흡수합니다. 그러나 뇌에 대한 이들의 결과는 제대로 이해되지 못했습니다. 따라서 임상 적으로 적절한 증상을 반복적으로 반복하는 단일 및 반복 mTBI의 동물 모델은 mTBI 및 뇌진탕의 연구를 발전시킬 수있는 수단을 제공합니다. 

비디오: A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

Normothermic 심장 마비와 심폐 소생술의 : 국소 빈혈 - Reperfusion 상해의 마우스 모델

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

연구

의학

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

PTSD의, 신경 Hematologic, 그리고 행동 상관 관계를 누설하는 행위에 대해서는 동물 모델에서 생체

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation.
Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB.

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

In vitro traumatic brain injury models are being developed to reproduce in vivo brain deformation. Stretch-induced injury has been employed for astrocytes, neurons, glial cells, aortic, and brain endothelial cells. However, our system uses a blood brain barrier (BBB) model that possesses properties constituting a legitimate model of the BBB to establish an in vitro&#160;TBI model.

로 뇌 미세 혈관 내피 세포 (CEnd를)에 기지개<em&gt; 체외</em혈액 뇌 장벽의&gt; 외상성 뇌 손상 모델

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the cornea, which can be caused by trauma, keratoplasty or infectious disease, breaks down the so called &lsquo;angiogenic privilege' of the cornea and forms the basis of multiple visual pathologies that may even lead to blindness. Although there are several treatment options available, the fundamental medical need presented by corneal neovascular pathologies remains unmet. In order to develop safe, effective, and targeted therapies, a reliable model of corneal NV and pharmacological intervention is required. Here, we describe an alkali-burn injury corneal neovascularization model in the mouse. This protocol provides a method for the application of a controlled alkali-burn injury to the cornea, administration of a pharmacological compound of interest, and visualization of the result. This method could prove instrumental for studying the mechanisms and opportunities for intervention in corneal NV and other neovascular disorders.

Neovascularization (NV) of the cornea can complicate multiple visual pathologies. Utilizing a controlled, alkali-burn injury model, a quantifiable level of corneal NV can be produced for mechanistic study of corneal NV and evaluation of potential therapies for neovascular disorders.

마우스의 각막 신생 혈관의 알칼리 화상 상해 모델

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the ...

Controlled Cortical Impact Model for Traumatic Brain Injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

외상성 뇌 손상에 대한 제어 피질 충격 모델

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable during renal transplantation. Experimental models that accurately and reproducibly recapitulate renal IRI are crucial in dissecting the pathophysiology of AKI and the development of novel therapeutic agents. Presented here is a mouse model of renal IRI that results in reproducible AKI. This is achieved by a midline laparotomy approach for the surgery with one incision allowing both a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia of the left kidney. By careful monitoring of the clamp position and body temperature during the period of ischaemia this model achieves reproducible functional and structural injury. Mice sacrificed 24 hr&#160;following surgery demonstrate loss of renal function with elevation of the serum or plasma creatinine level as well as structural kidney damage with acute tubular necrosis evident. Renal function improves and the acute tissue injury resolves during the course of 7 days following renal IRI such that this model may be used to study renal regeneration. This model of renal IRI has been utilized to study the molecular and cellular pathophysiology of AKI as well as analysis of the subsequent renal regeneration.

The mouse model of renal ischaemia reperfusion injury described here comprises of a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia that results in acute kidney injury. This model uses a midline laparotomy approach with all steps performed via one incision.

신장 허혈 재관류 상해 : 상해의 마우스 모델 및 재생

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable ...

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

청소년 쥐에 대한 가벼운 외상성 뇌 손상의 소설 모델

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor ...

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

신생아 마우스 척수 압축 부상 모델

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

A Repetitive Concussive Head Injury Model in Mice

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

마우스에 반복적 인 충격 포 헤드 손상 모델

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of ...

A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.

We introduce a tissue displacement-based contusive spinal cord injury model that can produce a consistent contusive spinal cord injury in adult mice.

마우스의 조직 변위에 근거한 척수 손상 모델

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between ...