Name: intracranial pressure monitoring in nontraumatic intraventricular hemorrhage rodent model
Uploaded: 2022-02-08T14:45:00
Description: Watch this Scientific Journal Video about Intracranial Pressure Monitoring In Nontraumatic Intraventricular Hemorrhage Rodent Model at JoVE.com

This work was funded by the NINDS grant: K08NS105914

All research methods and animal care/maintenance were performed in compliance with the institutional guidelines at the University of California, Davis. The Institutional Animal Care and Use Committee (IACUC) of the University of California, Davis, approved all animal use protocols and experimental procedures (IACUC protocol #21874).
1. Animal housing
<ol>
	<li>Obtain Sprague-Dawley rats of age 8-10 months old. Prior to any experimental procedure, house the rats in a vivarium...

<ol>
	<li>Gates, P. C., Barnett, H. J. M., Vinters, H. V., Simonsen, R. L., Siu, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Primary+intraventricular+hemorrhage+in+adults.">Primary intraventricular hemorrhage in adults.</a> Stroke. 17, 872-877 (1986).</li><li>Strajle, J., Garton, H. J. L., Maher, C. O., Muraszko, K., Keep, R. F., Xi, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+hydrocephalus+after+neonatal+and+adult+intraventricular+hemorrhage.">Mechanisms of hydrocephalus after neonatal and adult intraventricular hemorrhage.</a> Translational Stroke Research. 3, 25-38 (2012).</li><li>Murao, K., Rossi, C., Cordonnier, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracerebral+hemorrhage+and+cognitive+decline.">Intracerebral hemorrhage and cognitive decline.</a> Revue Neurologique. 169, 772-778 (2013).</li><li>Al-Khindi, T., Macdonald, R. L., Schweizer, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+and+functional+outcome+after+aneurysmal+subarachnoid+hemorrhage.">Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage.</a> Stroke. 41, 519-536 (2010).</li><li>Kreiter, K. T., 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=Predictors+of+cognitive+dysfunction+after+subarachnoid+hemorrhage.">Predictors of cognitive dysfunction after subarachnoid hemorrhage.</a> Stroke. 33, 200-208 (2002).</li><li>Zanaty, 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=Intraventricular+extension+of+an+aneurysmal+subarachnoid+hemorrhage+is+an+independent+predictor+of+a+worse+functional+outcome.">Intraventricular extension of an aneurysmal subarachnoid hemorrhage is an independent predictor of a worse functional outcome.</a> Clinical Neurology and Neurosurgery. 170, 67-72 (2018).</li><li>Gabrielian, L., Willshire, L. W., Helps, S. C., vanden Heuvel, C., Mathias, J., Vink, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracranial+pressure+changes+following+traumatic+brain+injury+in+rats:+lack+of+significant+change+in+the+absence+of+mass+lesions+or+hypoxia.">Intracranial pressure changes following traumatic brain injury in rats: lack of significant change in the absence of mass lesions or hypoxia.</a> Journal of Neurotrauma. 28, 2103-2111 (2011).</li><li>Kolar, M., Nohejlova, K., Duska, F., Mares, J., Pachl, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+of+cortical+perfusion+in+the+early+phase+of+subarachnoid+bleeding+in+a+rat+model+and+the+role+of+intracranial+hypertension.">Changes of cortical perfusion in the early phase of subarachnoid bleeding in a rat model and the role of intracranial hypertension.</a> Physiological Research. 66, 545-551 (2017).</li><li>Ariesen, M. J., Claus, S. P., Rinkel, G. J. E., Algra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+factors+for+intracerebral+hemorrhage+in+the+general+population.+A+systematic+review.">Risk factors for intracerebral hemorrhage in the general population. A systematic review.</a> Stroke. 34, 2060-2066 (2003).</li><li>MacLellan, C. L., Paquette, R., Colbourne, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+critical+appraisal+of+experimental+intracerebral+hemorrhage+research.">A critical appraisal of experimental intracerebral hemorrhage research.</a> Journal of Cerebral Blood Flow &amp; Metabolism. 32, 612-627 (2012).</li><li>Hartman, R., Lekic, T., Rojas, H., Tang, J., Zhang, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+functional+outcomes+following+intracerebral+hemorrhage+in+rats.">Assessing functional outcomes following intracerebral hemorrhage in rats.</a> Brain Research. 1280, 148-157 (2009).</li></ol>

This study investigated mechanisms to measure ICPs, MAPs, and CPPs in a nontraumatic IVH rat animal model. The results were recorded from the following groups: sham, VH 200 &#181;L, and vehicle control (artificial cerebrospinal fluid intraventricular injection) animals. This experimental design was chosen to investigate how ICPs can be monitored during IVH injection as we hypothesized that the spike in ICPs may contribute to the more significant secondary brain injury and thus memory deficit in IVH animal models. Therefo...

Intraventricular hemorrhage (IVH), a type of intracranial hemorrhage (ICH), is a devastating disease that carries significant mortality and morbidity. IVH is characterized as the accumulation of blood products inside the intracranial ventricles. Isolated IVH in uncommon and typically occurs in adults1. It may be associated with hypertensive hemorrhage, ruptured intracranial aneurysm or another vascular malformation, tumors, or trauma1. IVH leads to secondary brain injury as well as the development of hydrocephalus2. Survivors of IVH are often left with significant functional, memory, and cognitive impairments following their injury. These long-term cognitive and memory deficits are reported in as high as 44% of survivors of ICH3. In subarachnoid hemorrhage (SAH), another type of ICH, it is well known that approximately half of the survivors will have memory deficits, and for those who have IVH in addition to SAH, outcomes tend to be significantly worse4,5,6.
Underlying mechanisms of memory dysfunction following IVH remain to be elucidated. In vivo research utilizing nontraumatic IVH animal models with functional and memory dysfunction is essential in order to discover potential therapeutic targets for such patients. Animal models with more severe memory and functional dysfunction following IVH would be the best to study these changes. The senior author&#39;s lab has also been investigating specifically the role of high intracranial pressure (ICP) in the development of memory deficits in IVH rat models. Hence, methods to precisely measure ICPs during IVH were important to investigate. Herein, we report on methods of precisely measuring ICPs in an IVH rat model. Although ICP monitoring has previously been used in traumatic ICH as well as subarachnoid hemorrhage animal models, ICP monitoring in spontaneous IVH rodent&#160;models is not as commonly reported in the literature7,8. Hence, the experimental design presented herein included three groups of Sprague Dawley rats: sham, standard 200 &#181;l intraventricular hemorrhage, and vehicle control. For IVH group, an autologous intraventricular blood injection model was used. For vehicle control animals, intraventricular injection of sterile Lactated Ringer&#39;s solution was used. ICPs, mean arterial pressures (MAPs), and cerebral perfusion pressures (CPPs) were recorded intraoperatively, and results are reported herein.

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		<tr>
			<td>0.25% bupivacaine</td>
			<td>Hospira, Inc.</td>
			<td>409115901</td>
			<td></td>
		</tr>
		<tr>
			<td>1 mL syringe</td>
			<td>Covetrus</td>
			<td>60734</td>
			<td></td>
		</tr>
		<tr>
			<td>10% providine iodine solution</td>
			<td>Aplicare</td>
			<td>MSD093947</td>
			<td></td>
		</tr>
		<tr>
			<td>20 mL syringe</td>
			<td>Covidien</td>
			<td>8881520657</td>
			<td></td>
		</tr>
		<tr>
			<td>22 G needles</td>
			<td>Becton Dickinson</td>
			<td>305155</td>
			<td></td>
		</tr>
		<tr>
			<td>28 G intraventricular needles</td>
			<td>P technologies</td>
			<td>8IC313ISPCXC</td>
			<td>C313I/SPC 28-Gneedles to fit 22-G guide cannula with 6 mm projection</td>
		</tr>
		<tr>
			<td>3-0 silk suture</td>
			<td>Henry Schein, Inc.</td>
			<td>SP116</td>
			<td></td>
		</tr>
		<tr>
			<td>3-way-stopcock</td>
			<td>Merti Medical Systems</td>
			<td>M3SNC</td>
			<td></td>
		</tr>
		<tr>
			<td>4% paraformaldehyde</td>
			<td>Fisher Chemical</td>
			<td>30525-89-4</td>
			<td></td>
		</tr>
		<tr>
			<td>AnyMaze software</td>
			<td>Any-Maze behavioral tracking software</td>
			<td></td>
			<td>Stoelting CO, USA</td>
		</tr>
		<tr>
			<td>Artificial ointment</td>
			<td>Covetrus</td>
			<td>48272</td>
			<td></td>
		</tr>
		<tr>
			<td>Blood collection vials with EDTA</td>
			<td>Becton Dickinson</td>
			<td>367856</td>
			<td></td>
		</tr>
		<tr>
			<td>Bone wax</td>
			<td>CP Medical, Inc.</td>
			<td>CPB31A</td>
			<td></td>
		</tr>
		<tr>
			<td>Carprofen</td>
			<td>Zoetis, Inc.</td>
			<td>54771-8507-1</td>
			<td></td>
		</tr>
		<tr>
			<td>Centrifuge</td>
			<td>Beckman</td>
			<td>BE-GS6R</td>
			<td>Model GS-6R</td>
		</tr>
		<tr>
			<td>Cotton tip applicators</td>
			<td>Covetrus</td>
			<td>71214</td>
			<td></td>
		</tr>
		<tr>
			<td>Drill</td>
			<td>Dremel</td>
			<td>1600A011JA</td>
			<td></td>
		</tr>
		<tr>
			<td>Fiberoptic pressure sensors with readout units</td>
			<td>Opsens Medical</td>
			<td>OPP-M200-X-80SC- 2.0PTFE-XN-100PIT-P1 and LIS-P1-N-62SC</td>
			<td>Opp-M200 packaged pressure sensors with LifeSens system</td>
		</tr>
		<tr>
			<td>Forceps</td>
			<td></td>
			<td>11923-13, 11064-07</td>
			<td></td>
		</tr>
		<tr>
			<td>Gauze</td>
			<td>Covetrus</td>
			<td>71043</td>
			<td></td>
		</tr>
		<tr>
			<td>Guillotine</td>
			<td>World Precision Instruments</td>
			<td>51330</td>
			<td></td>
		</tr>
		<tr>
			<td>Heating pad with rectal thermometer</td>
			<td>CWE, Inc.</td>
			<td>08-13000 ,08-13014</td>
			<td>TC1000 Temperature controller</td>
		</tr>
		<tr>
			<td>Hemostats</td>
			<td></td>
			<td>&#160;13013-14,&#160; 13008-12</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Covetrus</td>
			<td>29405</td>
			<td></td>
		</tr>
		<tr>
			<td>Lactated ringers</td>
			<td>Baxter Healthcare Corp.</td>
			<td>Y345583</td>
			<td></td>
		</tr>
		<tr>
			<td>Laryngoscope</td>
			<td>American Diagnostic Corporation</td>
			<td>4080</td>
			<td></td>
		</tr>
		<tr>
			<td>Metal clip</td>
			<td>Fine Scientic Tools</td>
			<td>18056-14</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro scissors</td>
			<td>Fine Scientic Tools</td>
			<td>15007-08</td>
			<td></td>
		</tr>
		<tr>
			<td>Microscope</td>
			<td>Leica</td>
			<td>model L2</td>
			<td></td>
		</tr>
		<tr>
			<td>Needle driver</td>
			<td></td>
			<td>12003-15</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyethylene tubing</td>
			<td>Thermo Fisher Scientific</td>
			<td>14-170-12B</td>
			<td>PE-50 tubing</td>
		</tr>
		<tr>
			<td>Rats</td>
			<td>Envigo</td>
			<td></td>
			<td>Sprague Dawley rats 8&#8211;10 months old</td>
		</tr>
		<tr>
			<td>Scalpel</td>
			<td></td>
			<td>&#160;10010-00</td>
			<td></td>
		</tr>
		<tr>
			<td>Scissors</td>
			<td></td>
			<td>14090-11</td>
			<td></td>
		</tr>
		<tr>
			<td>Stereotaxic instrument</td>
			<td>Kopf instruments</td>
			<td></td>
			<td>Model 940 with ear bars</td>
		</tr>
		<tr>
			<td>Syringe pump</td>
			<td>KD Scientific</td>
			<td>780100</td>
			<td>Model 100 series</td>
		</tr>
		<tr>
			<td>Touhy Borst</td>
			<td>Abbott</td>
			<td>23242</td>
			<td></td>
		</tr>
		<tr>
			<td>Ventilator</td>
			<td>Harvard rodent ventilator</td>
			<td>55-0000</td>
			<td>Model 683</td>
		</tr>
	</tbody>
</table>

intracranial pressure monitoring in nontraumatic intraventricular hemorrhage rodent model

Survivors of intraventricular hemorrhage are often left with significant long-term memory impairment; thus, research utilizing intraventricular hemorrhage animal models is essential. In this study, we sought out ways to measure intracranial pressure, mean arterial pressure, and cerebral perfusion pressure during nontraumatic intraventricular hemorrhage in rats. The experimental design included three Sprague Dawley groups: sham, standard 200 &#181;l intraventricular hemorrhage, and vehicle control groups. By introducing an intraparenchymal fiberoptic pressure sensor, precise intracranial pressure measurements were obtained in all groups. Cerebral perfusion pressures were calculated with the knowledge of intracranial pressure and mean arterial pressure values. As expected, the intraventricular hemorrhage and vehicle control groups both experienced a rise in the intracranial pressure and subsequent decline in cerebral perfusion pressure during intraventricular injection of autologous blood and artificial cerebrospinal fluid, respectively. The addition of an intraparenchymal fiberoptic pressure sensor is beneficial in monitoring precise intracranial pressure changes.

Intracranial, mean arterial, and cerebral perfusion pressures 
Both ICPs and MAPs were monitored intraoperatively in all animals (Figure 1). Rats were of 8-10 months old with a mean weight of 495 &#177; 17 g. Real-time ICP graphs were also collected (Figure 2). Excluding the sham group, ICPs increased significantly during intraventricular injection in IVH as well as vehicle control groups (Figure 3). I...

Watch this Scientific Journal Video about Intracranial Pressure Monitoring In Nontraumatic Intraventricular Hemorrhage Rodent Model at JoVE.com

Intracranial Pressure Monitoring In Nontraumatic Intraventricular Hemorrhage Rodent Model

Monitoring intracranial pressure in rodent&#160;models of nontraumatic intraventricular hemorrhage is not common in the current literature. Herein, we demonstrate a technique for measuring intracranial pressure, mean arterial pressure, and cerebral perfusion pressure during intraventricular hemorrhage in a rat&#160;animal model.

Survivors of intraventricular hemorrhage are often left with significant long-term memory impairment; thus, research utilizing intraventricular hemorrhage ...

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