이 작품은 국립 보건원 (R01DK58096 빈센트 Poitout까지)에 의해 지원되었다. 빈센트 Poitout은 당뇨병과 췌장 베타 세포 기능에있는 캐나다 연구 의자를 보유하고 있습니다. 베이더 Zarrouki 머크와 일라이 릴리에서 박사 후 장학금을 받았다. Ghislaine의 FONTES는 캐나다 당뇨병 협회에서 박사 후 친교에 의해 지원되었다.

개요, 7 일 회복 기간을 허용, 회전 및 케이지에서 자유롭게 이동하는 동물의 수 평형 시스템을 사용하여 펌프에 카테터를 연결하는 절차는 전신 마취하에 우측 경정맥 정맥과 왼쪽 경동맥을 catheterizing으로 구성 72 시간 동안 (헤파린 9 주입 할 때 포화 지방산 약 80 % unsaturated/20 %의 혼합물을 생성하는 콩 오일 에멀젼) 포도당 및 / 또는 Intralipid을 주입. 1. 오른쪽 경정맥 정맥과 좌측 경동맥의 Canulation <ol><li> 수술기구를 소독. Canulation 튜브는 절차 이전에 액체 살균 에이전트 (2.6 % 글루 타르 알데히드)를 사용하여 콜드 소독해야합니다. 16-24 시간 동안 멸균 용기에 튜브를 담가. 린스 사용하기 전에 글루 타르 알데히드의 모든 흔적을 제거하는 멸균 증류수로 충분히 세척하십시오. </li><li> 계산 쥐 무게약물 복용량 : Carprofen 5 ㎎ / ㎏ : 희석 1 / 10 = 본체 무게 (g) × 0.001 ML SC (진통제) 0.01 ㎎ / ㎏ Glycopyrrolate : 희석 1 / 10 = BW (G) X 0.0012 ML SC (항콜린) </li><li> isoflurane을하고 산소를 사용하여 쥐를 마취. </li><li> 그 배에서 쥐를 놓습니다. 어깨의 기초에 귀 뒤에 영역을 면도. 그 뒷면에있는 쥐를 놓습니다. 앞발로 목 아래의 지역을 면도. </li><li> 클로르헥시딘, 알코올, 요오드와 준비는 수술 부위. 약물을 관리 할 수​​ 있습니다. </li><li> 수술 필드에 쥐를 전송합니다. </li><li> 무균 기술을 사용하여, 오른쪽 경정맥 정맥 헤파린 생리 식염수 5 U로 채워진 1 ML의 주사기에 부착 된 PE-50 canula 함께 왼쪽 경동맥을 canulate. 복구 기간 동안 응고 방지하기 위해 헤파린 생리 식염수 50 U와 canulas을 세척하십시오. 무딘 23G 바늘을 사용합니다. 23G 핀 각 canula를 닫습니다. </li><li> 수술 후, 오프 약 2.5 mm 트림아래 앞니와 장소 먹게되는 canulas을 방지하기 위해 주입 재킷 쥐. </li><li> isoflurane을 대피에 도움이 산소를 (1 L / 10 분 분) 제공합니다. </li><li> 완전히 깨어 때까지 가열 새장에 쥐를 놓습니다. </li><li> 주입 조건 당 하나를 사용하는 네 쥐 (표 1)를 운영하고 있습니다. </li></ol> 2. 수술 후 관리 (카테터의 사후 수술 치료 및 연결) <ol><li> 1 일 및 2 일 후 수술에 쥐 무게. </li><li> 1 일 후 수술에 한 번 하루에 2 수술 후 두 번 glycopyrrolate (BW (g) × 0.00048 ML) SC를 관리 할 수​​ 있습니다. </li><li> 필요한 경우 추가 지원 치료를 관리 할 수​​ 있습니다 : 유체 가열 패드, 젖은 다이어트, 산소 치료, 진통제, 항콜린. </li><li> 7 일 후 수술에 주입을위한 유량을 계산하기 위해 쥐를 무게. </li><li> 케이지 그릴 상단 (그림 1)에 장착 밧줄과 회전을 사용하여 주입 시스템에 각 쥐를 연결합니다.</li><li> 혈전을 제거하는 헤파린 생리 식염수 5 U와 canulas을 세척하십시오. 응고 방지하기 위해 헤파린 생리 식염수 50 U와 함께 한 번 더 canulas을 세척하십시오. </li><li> 쥐가 밧줄에 적응하고 주입을 시작하기 전에 적어도 24 시간 동안 회전 할 수 있습니다. </li></ol> 3. 주입 <ol><li> 각 쥐​​를 측정 혈당의 동맥에서 혈액의 0.15 ML을 그립니다. 경정맥 canulas를 세척합니다. 각 쥐​​의 두 canulas의 응고를 방지하기 위해 헤파린 생리 식염수 50 U를 사용합니다. </li><li> 2 % EDTA를 포함하는 0.5 ML 수집 튜브에 혈액 샘플을 전송합니다. 2 분 동안 10,000 rpm으로 원심 분리 -20 ° C.에서 플라즈마를 동결 </li><li> 아래의 주입 조건 각각에 대해 두 개의 60 ML 주사기를 채우십시오. 펌프의 뒤쪽 위치에 펌프 및 장소 주사기 2의 전면 위치에 자리 주사기 1. </li><li> Y-커넥터와 멸균 된 CO-EX T22 튜브와 함께 솔루션의 각 쌍에 가입하세요. 하버드 33 주사기를 놓고이중 주사기 펌프. </li><li> 케이지 바닥을 변경하고 케이지 그릴 상단에서 모든 음식을 제거합니다. </li><li> 케이지 그릴 상단에 150 표준 차우의 G와 장소를 무게. </li><li> 케이지 그릴 회전에 주사기를 연결합니다. 라인에서 갇힌 공기를 제거하는 제대로 주사기를 세척하십시오. </li><li> 주입 시스템에 쥐를 연결하기 전에 찍은 체중을 사용하여 주입 유량을 계산합니다. 환율은 ML / H에 포도당 주입 속도 (GIR)을 변환하는 Microsoft Excel 파일로 계산됩니다. </li><li> 제조업체의 설정에 따라 60 ML의 주사기에 대한 흐름 속도를 관리하는 펌프를 설정합니다. 주사기 1 (전면 주사기)를위한 속도와 주사기 2 (뒤 주사기)에 대한 비율을 입력합니다. </li><li> 펌프를 시작합니다. </li></ol> 4. 모니터링 <ol><li> 펌프를 시작한 후, 아무 회전이나 canulas에서 유출하고 주입 튜브가 꼬여 있지 않은가 없는지 확인합니다. 도 기포가 없는지 확인합니다튜브. </li><li> 주입 3 시간 후 혈당을 모니터링하기 위해 혈액 샘플을 채취. , 24, 10 후 48를 반복 주입의 72 시간. 예방 조치로, 혈당은 주입 후 30, 34, 54, 60 시간 후 모니터링됩니다. 혈당은 휴대용 혈당 모니터를 사용하여 전체 혈액 한 방울을 사용하여 측정 할 수 있습니다. 이 주입 동안 그려 혈액의 양을 제한하기 때문에 크게 변경 혈액량 및 / 또는 혈소판을 방지합니다. </li><li> 주사기 1 비율은 220-250 밀리그램 / DL에서 혈당을 유지하기 위해 혈당 값에 따라 수정됩니다. 유리 지방산은 1 mmol / L로 유지되기 때문에 주사기 2의 비율은 주입 72 시간 동안 변경되지 않습니다 </li><li> 주입 조건은 대조군에 대해 수신 볼륨이 실험 동물 (표 1)에 대해 수신 볼륨에 해당하므로 쌍입니다. </li><li> 주입 24 시간 후, 케이지 바닥을 변경하고 케이지 그릴에 남아있는 음식을 무게. 먹지 부분 t를 반환케이지 그릴 O를. 48 시간 후 반복합니다. </li><li> 리필 주사기 매일 같이 주입 72 시간 동안 필요합니다. </li><li> 주입하는 동안 항상 염증이나 불편 함이 없는지 쥐를 관찰합니다. 필요한 경우 적절한 치료를 관리 할 수​​ 있습니다. </li></ol> 5. 후 주입 안락사 <ol><li class="jove_content"> 주입 72 시간 후, 쥐가 케타민을 / xylazine 칵테일 (182 마취제와 11.6 ㎎ / ㎏이 ㎎ / xylazine kg의 0.9 % 염화나트륨과 1:2 희석)의 0.5 ML로 정맥 마취 있습니다. </li><li class="jove_content"> 발가락 핀치 반사는 마취의 수준을 확인하는 데 사용됩니다. 추가 마취는 필요에 따라 관리됩니다. </li><li class="jove_content"> 쥐가 마취되면 복강 수술 가위로 열립니다. 쥐가 대동맥이나 대정맥에서 주사기 혈액의 15 ML을 그려 exsanguinated 있습니다. </li></ol>

<ol>
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Metab Care. 13, 382-390 (2010).</li><li>Cusi, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+obesity+and+lipotoxicity+in+the+development+of+nonalcoholic+steatohepatitis:+pathophysiology+and+clinical+implications.">Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications.</a> Gastroenterology. 142, 711-725 (2012).</li></ol>

빈센트 Poitout 공동 창립자이며 Bêtagenex 주식 회사, 상업 서비스로이 문서에서 제시된 주입 모델을 제공하는 계약 연구 기관에서 연구 계약을 받았다.

이전 연구의 숫자가 우리의 지식 만성 포도당 주입 (예 : 10-15) 또는 설치류의 지질 (예 : 16, 17)을 고용하고 있지만 두 연료의 혼합 투여는 생쥐 18보고되었다. 여기에 제시된 만성 주입 모델은 쥐의 생물학적 기능의 다양한 영양소 과잉에 미치는 영향을 연구하는 여러 가지 이점을 제공합니다. 첫째, 유 전적으로 비만 설치류를 포함하지 않으며, 인간의 일반적?...

순환 포도당과 지질의 만성 높은 수준을 포함​​ 포도당 항상성의 유지에 연루 여러 장기의 기능을 변경하여 제 2 형 당뇨병의 병인에 기여하는 제안 국한되지 않은, 췌장 베타 세포 (리뷰 1). 만성 고혈당증 따라서 악순환을 만들고 제 2 형 당뇨병 환자에서 혈당 조절의 악화에 기여 첫 번째 장소에서 혈당 상승을 준 베타 세포 결함을 악화하는 glucotoxicity 가설 posits. 마찬가지로, glucolipotoxicity 가설은 주로 제 2 형 당뇨병에서 관찰 포도당과 지질 수준을 수반 상승은, 베타 세포에 해로운 것을 제안한다. 췌장 베타 세포 기능에 만성적으로 높은 영양소의 해로운 효과의 세포 및 분자 메커니즘을 해독하는 u​​nderstandi의 열쇠입니다제 2 형 당뇨병 1의 병인의 NG. 이를 위해 많은 연구가 랑게르한스의 고립 된 섬이나 클론, 인슐린 분비 세포 라인에 체외에서 만성 영양 과잉 전직 생체의 메커니즘을 조사했다. 배양 세포 나 섬에서 사용되는 지방산의 농도는 거의 생체 2의 베타 세포의 주변에 순환 수준을 일치하지 않기 때문에, 전체 유기체 이러한 모델 시스템에서 얻은 결과의 번역은 특히 복잡합니다. 반면에, 영양 과잉의 질문에 답변 베타 세포 장애의 메커니즘으로 주커 당뇨병 지방간 쥐 3,4, 햄스터 Psammomys obesus 5와 높은 지방 다이어트 -에 의해 예시, 당뇨병의 설치류 모델에서 조사 된 공급 마우스 6. 이 모델은, 그러나, 고유 신진 대사 이상에 의해 특징과 혈액 포도당의 조작에 쉽게 순종하지는 않습니다및 / 또는 더 많은 통제와 적은 만성 설정 지질 수준. 그렇지 않으면 정상 동물의 일 기간에 영양소 수준을 순환 변경할 수 있도록, 우리는 생리적 매개 변수 및 함수에 우리가 단독으로 또는 조합, 지질 및 포도당의 영향을 조사 할 수 정상 쥐의 만성 주입 모델을 개발 7,8.

<table border="1">
		<tbody>
		 <tr>
			<td>Name of Reagent/Material</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		 </tr>
		 <tr>
			<td>Saline 0.9%</td>
			<td>BD</td>
			<td>JB1324</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Dextrose 70%</td>
			<td>McKesson</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Intralipid 20%</td>
			<td>Fresenius Kabi</td>
			<td>JB6023</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Metricide (Glutaraldehyde 2.6%)</td>
			<td>Metrex</td>
			<td>11-1401</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Heparin Sodium 10,000 USP u/ml</td>
			<td>PPC</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Carprofen</td>
			<td>Metacam</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Glycopyrrolate</td>
			<td>Sandoz</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Isoflurane</td>
			<td>Abbott</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Chlohexidine 2%</td>
			<td></td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Alcohol 70%</td>
			<td></td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Iodine</td>
			<td></td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>PE-50</td>
			<td>BD</td>
			<td>427411</td>
			<td></td>
		 </tr>
		 <tr>
			<td>CO-EX T22</td>
			<td>Instech Solomon</td>
			<td>BCOEX-T22</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Connector 22G</td>
			<td>Instech Solomon</td>
			<td>SC22/15</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Swivel 22G</td>
			<td>Instech Solomon</td>
			<td>375/22PS</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Y-Connector 22G</td>
			<td>Instech Solomon</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Counterbalance and arm</td>
			<td>Instech Solomon</td>
			<td>CM375BP</td>
			<td></td>
		 </tr>
		 <tr>
			<td>23 G blunted needles</td>
			<td>Instech Solomon</td>
			<td>LS23</td>
			<td></td>
		 </tr>
		 <tr>
			<td>23 G canulation pins</td>
			<td>Instech Solomon</td>
			<td>SP23/12</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Tethers (12 inch)</td>
			<td>Lomir</td>
			<td>RT12D</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Infusion jackets </td>
			<td>Lomir</td>
			<td>RJ01, RJ02, RJ03, RJ04</td>
			<td></td>
		 </tr>
		 <tr>
			<td>(SM-XL)</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Tether attachment piece</td>
			<td>Lomir</td>
			<td>RS T1</td>
			<td></td>
		 </tr>
		 <tr>
			<td>60 ml syringe</td>
			<td>BD</td>
			<td>309653</td>
			<td></td>
		 </tr>
		 <tr>
			<td>1 ml syringe</td>
			<td>BD</td>
			<td>309602</td>
			<td></td>
		 </tr>
		</tbody>
 </table>

a model of chronic nutrient infusion in the rat

영양소의 과도한 수준에 만성 노출은 여러 장기와 조직의 기능에 영향을 미치는 비만과 관련된 여러 합병증의 개발과 제 2 형 당뇨병 등의 대사 증후군에 기여할 것으로 가정합니다. 포도당과 지방산의 과도한 수준은 췌장 베타 세포와 인슐린의 분비에 영향을 미치는하는 메커니즘을 연구하기 위해, 우리는 쥐의 만성 영양 주입 모델을 설립했다. 7 일 회복 기간을 허용; 회전과 케이지에서 자유롭게 이동하는 동물의 수 평형 시스템을 사용하여 펌프에 카테터를 연결하고 주입 절차는 전신 마취하에 우측 경정맥 정맥과 왼쪽 경동맥을 catheterizing으로 구성 포도당 및 / 또는 Intralipid (헤파린 주입하면 약 80 % unsaturated/20 % 포화 지방산의 혼합물을 생성하는 콩 오일 에멀젼) 72 시간 동안. 이 모델은 여러 가지 ADVANTA을 제공합니다약물 화합물을 공동으로 주입 할 수있는 옵션, 그리고식이 모델에 반대 비교적 짧은 시간 프레임 정밀 포도당과 지방산 순환의 목표 수준을 조절 할 수있는 가능성 등 GES. 그것은 장기의 다양한 영양소에 의한 장애의 메커니즘을 검토하고, 이러한 맥락에서 약물의 효과를 테스트하는 데 사용할 수 있습니다.

수술을 시행 한 42 쥐의 일련의 밖으로 5 쥐가 수술 후 기간 동안 손실 된 1 쥐가 86 %의 성공률을 나타내는 주입하는 동안 끊어졌습니다. 결국 주입 된 37 쥐의 평균 체중은 608이었다 ± 5 수술 전 g 및 588 ± 주입 개시 6 개의 G (평균 ± SE, N = 37, P &lt;0.0001로 t-test를 쌍).에게 72 시간 주입 기간 동안 식염수 (SAL) 및 + Intralipid (GLU + IL) 그림 2A와 2B 쇼 혈액 포도당과 지방산 수준은 각각 포도당 :. ?...

Watch this Scientific Journal Video about A Model of Chronic Nutrient Infusion in the Rat at JoVE.com

A Model of Chronic Nutrient Infusion in the Rat

쥐의 혈당과 Intralipid 만성 주입을위한 프로토콜이 설명되어 있습니다. 이 모델은 기관의 기능과 생리 학적 매개 변수에 대한 영양 과잉의 영향을 연구하는 데 사용할 수 있습니다.

쥐의 만성 영양 주입의 모델

Chronic exposure to excessive levels of nutrients is postulated to  affect the function of several organs and tissues and to contribute to the  ...

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Research

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Medicine

12.6K 조회수.  CRCHUM. 쥐의 혈당과 Intralipid 만성 주입을위한 프로토콜이 설명되어 있습니다. 이 모델은 기관의 기능과 생리 학적 매개 변수에 대한 영양 과잉의 영향을 연구하는 데 사용할 수 있습니다.

비디오: A Model of Chronic Nutrient Infusion in the Rat

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

Orthotopic 대동맥 이식 : 만성 Vasculopathy의 개발 연구에 생쥐 모델

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

연구

의학

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

쥐의 방광 통증 모델로 방광 팽창 유발 내장 운동 응답

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions

Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these diseases. Chronic retinal diseases such as retinal oedema or neovascularization usually require multiple intraocular injections to effectively treat the condition. However, the risks associated with these injections increase with repeated delivery of the drug. Therefore, alternative delivery methods need to be established in order to minimize the risks of reinjection. Several other investigations have developed methods to deliver drugs over extended time, through materials capable of releasing chemicals slowly into the eye. In this investigation, we outline the use of Elvax 40W, a copolymer resin, to act as a vehicle for drug delivery to the adult rat retina. The resin is made and loaded with the drug. The drug-resin complex is then implanted into the vitreous cavity, where it will slowly release the drug over time. This method was tested using 2-amino-4-phosphonobutyrate (APB), a glutamate analogue that blocks the light response of the retina. It was demonstrated that the APB was slowly released from the resin, and was able to block the retinal response by 7 days after implantation. This indicates that slow-release drug delivery using this copolymer resin is effective for treating the retina, and could be used therapeutically with further testing.

This paper details how Elvax 40W can be used as a slow-release method for drug delivery to the adult rat retina. The protocol for preparing, loading, and delivering the drug-resin complex to the eye is described.

쥐의 망막에 Elvax 40W를 통해 서방 약물 전달 : 만성 질환의 치료를위한 시사점

Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these ...

Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps

Decline in hippocampal-dependent explicit memory (memory for facts and events) is one of the earliest clinical symptom of Alzheimer&#39;s disease (AD). It is well established that synapse loss and ensuing neurodegeneration are the best predictors for memory impairments in AD. Latest studies have emphasized the neurotoxic role of soluble amyloid-beta oligomers (A&#946;o) that begin to accumulate in the human brain approximately 10 to 15 yr before the clinical symptoms become apparent. Many reports indicate that soluble A&#946;o correlate with memory deficits in AD models and humans. The A&#946;o-induced neurodegeneration observed in neuronal and brain slice cultures has been more challenging to reproduce in many animal models. The model of repeated A&#946;o infusions shown here overcome this issue and allow addressing two key domains for developing new disease modifying therapies: identify biological markers to diagnose early AD, and determine the molecular mechanisms underpinning A&#946;o-induced memory deficits at the onset of AD. Since soluble A&#946;o aggregate relatively fast into insoluble A&#946; fibrils that correlate poorly with the clinical state of patients, soluble A&#946;o are prepared freshly and injected once per day during six days to produce marked cell death in the hippocampus. We used cannula specially design for simultaneous infusions of A&#946;o and continuous infusion of A&#946;o antibody (6E10) in the hippocampus using osmotic pumps. This innovative in vivo method can now be used in preclinical studies to validate the efficiency of new AD therapies that might prevent the deposition and neurotoxicity of A&#946;o in pre-dementia patients.

To study the effects of A&#946;o in vivo, we developed a model based on repeated hippocampal infusions of soluble A&#946;o coupled with continuous infusion of A&#946;o antibody (6E10) in the hippocampus using osmotic pumps to counteract the neurotoxic effect of A&#946;o.

만성 아밀로이드 - 베타 올리고머 주입의 동물 모델에서 신경 퇴행은 삼투 펌프와 항체 치료 인 퓨즈에 의해 상쇄되어

Decline in hippocampal-dependent explicit memory (memory for facts and events) is one of the earliest clinical symptom of Alzheimer&#39;s disease (AD). It ...

Use of a Central Venous Line for Fluids, Drugs and Nutrient Administration in a Mouse Model of Critical Illness

This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce sepsis with the use of a central venous line for fluids, drugs and nutrient administration to mimic the human clinical setting. Critically ill patients require intensive medical support in order to survive. While the majority of patients will recover within a few days, about a quarter of the patients need prolonged intensive care and are at high risk of dying from non-resolving multiple organ failure. Furthermore, the prolonged phase of critical illness is hallmarked by profound muscle weakness, and endocrine and metabolic changes, of which the pathogenesis is currently incompletely understood. The most widely used animal model in critical care research is the cecal ligation and puncture model to induce sepsis. This is a very reproducible model, with acute inflammatory and hemodynamic changes similar to human sepsis, which is designed to study the acute phase of critical illness. However, this model is hallmarked by a high lethality, which is different from the clinical human situation, and is not developed to study the prolonged phase of critical illness. Therefore, we adapted the technique by placing a central venous catheter in the jugular vein allowing us to administer clinically relevant supportive care, to better mimic the human clinical situation of critical illness. This mouse model requires an extensive surgical procedure and daily intensive care of the animals, but it results in a relevant model of the acute and prolonged phase of critical illness.

This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce sepsis with the use of a central venous line for fluids, drugs and nutrient administration to mimic the human clinical setting.

위독한 병의 마우스 모델에서 유체, 약물 및 영양 관리를위한 중심 정맥 라인의 사용

This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

Myography 와이어를 사용 하 여 마우스 Mesenteric 동맥의 isometric 수축 측정

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

A New Best Practice for Validating Tail Vein Injections in Rat with Near-infrared-Labeled Agents

Intravenous (IV) administration of agents into the tail vein of rats can be both difficult and inconsistent. Optimizing tail vein injections is a key part of many experimental procedures where reagents need to be introduced directly into the bloodstream. Unwittingly, the injection can be subcutaneous, possibly altering the scientific outcomes. Utilizing a nanoemulsion-based biological probe with an incorporated near-infrared fluorescent (NIRF) dye, this method offers the capability of imaging a successful tail vein injection in vivo. With the use of a NIRF imager, images are taken before and after the injection of the agent. An acceptable IV injection is then qualitatively or quantitatively determined based on the intensity of the NIRF signal at the site of injection.

Here we present a method to validate tail vein injections in rats by utilizing near-infrared fluorescence imaging data from dyes incorporated into agents or biological probes. The tail is imaged before and after the injection, the fluorescent signal is quantified, and an assessment of the injection quality is made.

근처-적외선-표시 에이전트와 쥐의 꼬리 정 맥 주사의 유효성 검사에 대 한 새로운 좋습니다

Intravenous (IV) administration of agents into the tail vein of rats can be both difficult and inconsistent. Optimizing tail vein injections is a key part ...

Acupuncture in a Rat Model of Asthma

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes methods for the fabrication of the high platform, establishes a rat model of asthma and measures changes in respiratory function using a noninvasive and real-time whole-body plethysmography (WBP) system.

천식의 쥐 모형에 있는 침술

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes ...

A Mouse Model for Chronic Pancreatitis via Bile Duct TNBS Infusion

Chronic pancreatitis (CP) is a complex disease involving pancreatic inflammation and fibrosis, glandular atrophy, abdominal pain and other symptoms. Several rodent models have been developed to study CP, of which the bile duct 2,4,6 -trinitrobenzene sulfonic acid (TNBS) infusion model replicates the features of neuropathic pain seen in CP. However, bile duct drug infusion in mice is technically challenging. This protocol demonstrates the procedure of bile duct TNBS infusion for generation of a CP mouse model. TNBS was infused into the pancreas through the ampulla of Vater in the duodenum. This protocol optimized drug volume, surgical techniques, and drug handling during the procedure. TNBS-treated mice showed features of CP as reflected by bodyweight and pancreas weight reductions, changes in pain-associated behaviors, and abnormal pancreatic morphology. With these improvements, mortality associated with TNBS injection was minimal. This procedure is not only critical in generating pancreatic disease models but is also useful in local pancreatic drug delivery.

Chronic pancreatitis (CP) is a disease characterized by inflammation and fibrosis of the pancreas, often associated with intractable abdominal pain. This article focuses on refining the technique to generate a mouse model of CP via bile duct infusion with 2,4,6 -trinitrobenzene sulfonic acid (TNBS).

담즙 덕트 TNBS 주입을 통한 만성 췌장염을 위한 마우스 모델

Chronic pancreatitis (CP) is a complex disease involving pancreatic inflammation and fibrosis, glandular atrophy, abdominal pain and other symptoms. ...

쥐 모델에서 FSN 요법 개선: 불편함 최소화 및 효율성 극대화

Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the mechanisms of action are still not fully understood. During FSN treatment, the FSN needle is inserted and retained in the subcutaneous tissues for a long duration with a swaying movement. However, challenges arise from maintaining a posture while manipulating FSN in animal models (e.g., rats) for researchers. Uncomfortable treatment can lead to fear and resistance to FSN needles, increasing the risk of injury and may even affect research data. Anesthesia may also affect the study results too. Hence, there is a need for strategies in FSN therapy on animals that minimize injury during the intervention. This study employs a chronic constriction injury model in Sprague-Dawley rats to induce neuropathic pain. This model replicates the pain induced by nerve injury observed in humans through surgical constriction of a peripheral nerve, mimicking the compression or entrapment seen in conditions such as nerve compression syndromes and peripheral neuropathies. We introduce an appropriate manipulation for easily inserting an FSN needle into the subcutaneous layer of the animal&#39;s body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat&#39;s discomfort prevents the rat from being tense, which causes the muscle to contract and hinder the entry of the needle and improves the study efficiency.

저자 스포트라이트: FSN 치료의 치료 효과 발표 – 신경병증성 통증의 연구 및 임상 적용 연결

We present a protocol for using Fu's subcutaneous needling in a chronic constriction injury model to induce sciatic nerve pain in rats.

좌골 신경통에 대한 Fu의 피하 침의 효능: 만성 수축 손상 쥐 모델의 행동 및 전기 생리학적 변화

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the ...