TY - JOUR

T1 - Subacute phase of subarachnoid haemorrhage in female rats: Increased intracranial pressure, vascular changes and impaired sensorimotor function

AU - Spray, Stine

AU - Haanes, Kristian Agmund

AU - Edvinsson, Lars

AU - Johansson, Sara Ellinor

PY - 2021

Y1 - 2021

N2 - Objective: Early brain injury (EBI) and delayed cerebral ischemia (DCI) after subarachnoid haemorrhage (SAH) has devastating consequences but therapeutic options and the underlying pathogenesis remain poorly understood despite extensive preclinical and clinical research. One of the drawbacks of most preclinical studies to date is that the mechanisms behind DCI after SAH are studied only in male animals. In this study we therefore established a female rat model of SAH in order to determine subacute pathophysiological changes that may contribute to DCI in females. Methods: Experimental SAH was induced in female rats by intracisternal injection of 300 μL of autologous blood. Sham operation served as a control. Neurological deficits and intracranial pressure measurements were evaluated at both 1 and 2 days after surgery. Additionally, changes in cerebral vascular contractility were evaluated 2 days after surgery using wire myography. Results: SAH in female rats resulted in sensorimotor deficits and decreased general wellbeing on both day 1 and day 2 after SAH. Intracranial pressure uniformly increased in all rats subjected to SAH on day 1. On day 2 the intracranial pressure had increased further, decreased slightly or remained at the level seen on day 1. Furthermore, female rats subjected to SAH developed cortical brain edema. Cerebral arteries, isolated 2 days after SAH, exhibited increased vascular contractions to endothelin-1 and 5-carboxamidotryptamine. Conclusion: In the subacute phase after SAH in female rats, we observed increased intracranial pressure, decreased wellbeing, sensorimotor deficits, increased vascular contractility and cortical brain edema. Collectively, these pathophysiological changes may contribute to DCI after SAH in females. Previous studies reported similar pathophysiological changes for male rats in the subacute phase after SAH. Thus, prevention of these gender-independent mechanisms may provide the basis for a universal treatment strategy for DCI after SAH. Nevertheless, preclinical studies of potential therapies should employ both male and female SAH models.

AB - Objective: Early brain injury (EBI) and delayed cerebral ischemia (DCI) after subarachnoid haemorrhage (SAH) has devastating consequences but therapeutic options and the underlying pathogenesis remain poorly understood despite extensive preclinical and clinical research. One of the drawbacks of most preclinical studies to date is that the mechanisms behind DCI after SAH are studied only in male animals. In this study we therefore established a female rat model of SAH in order to determine subacute pathophysiological changes that may contribute to DCI in females. Methods: Experimental SAH was induced in female rats by intracisternal injection of 300 μL of autologous blood. Sham operation served as a control. Neurological deficits and intracranial pressure measurements were evaluated at both 1 and 2 days after surgery. Additionally, changes in cerebral vascular contractility were evaluated 2 days after surgery using wire myography. Results: SAH in female rats resulted in sensorimotor deficits and decreased general wellbeing on both day 1 and day 2 after SAH. Intracranial pressure uniformly increased in all rats subjected to SAH on day 1. On day 2 the intracranial pressure had increased further, decreased slightly or remained at the level seen on day 1. Furthermore, female rats subjected to SAH developed cortical brain edema. Cerebral arteries, isolated 2 days after SAH, exhibited increased vascular contractions to endothelin-1 and 5-carboxamidotryptamine. Conclusion: In the subacute phase after SAH in female rats, we observed increased intracranial pressure, decreased wellbeing, sensorimotor deficits, increased vascular contractility and cortical brain edema. Collectively, these pathophysiological changes may contribute to DCI after SAH in females. Previous studies reported similar pathophysiological changes for male rats in the subacute phase after SAH. Thus, prevention of these gender-independent mechanisms may provide the basis for a universal treatment strategy for DCI after SAH. Nevertheless, preclinical studies of potential therapies should employ both male and female SAH models.

KW - 5-hydroxytryptamine

KW - Cortical brain edema

KW - Endothelin-1

KW - Female rats

KW - Increased vasoconstriction

KW - Intracranial pressure

KW - Neurological deficits

KW - Subarachnoid haemorrhage

U2 - 10.1016/j.mvr.2020.104127

DO - 10.1016/j.mvr.2020.104127

M3 - Tidsskriftartikel

C2 - 33359306

VL - 135

JO - Microvascular Research

JF - Microvascular Research

SN - 0026-2862

M1 - 104127

ER -