Intracranial Pressure Monitoring In Nontraumatic Intraventricular Hemorrhage Rodent Model

Summary

Monitoring intracranial pressure in rodent 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 animal model.

Abstract

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 µl 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.

Introduction

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 worse^4,5,6.

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'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 models is not as commonly reported in the literature^7,8. Hence, the experimental design presented herein included three groups of Sprague Dawley rats: sham, standard 200 µl 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's solution was used. ICPs, mean arterial pressures (MAPs), and cerebral perfusion pressures (CPPs) were recorded intraoperatively, and results are reported herein.

Protocol

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 Obtain Sprague-Dawley rats of age 8-10 months old. Prior to any experimental procedure, house the rats in a vivarium…

Representative Results

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 ± 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…

Discussion

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 µL, 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…

Materials

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