Long-Term Functional Consequences and Ongoing Cerebral Inflammation after Subarachnoid Hemorrhage in the Rat

Abstract

Subarachnoid hemorrhage (SAH) represents a considerable health problem with an incidence of 6–7 per 100.000 individuals per year in Western society. We investigated the long-term consequences of SAH on behavior, neuroinflammation and gray- and white-matter damage using an endovascular puncture model in Wistar rats. Rats were divided into a mild or severe SAH group based on their acute neurological score at 24 h post-SAH. The degree of hemorrhage determined in post-mortem brains at 48 h strongly correlated with the acute neurological score. Severe SAH induced increased TNF-α, IL-1β, IL-10, MCP-1, MIP2, CINC-1 mRNA expression and cortical neutrophil influx at 48 h post-insult. Neuroinflammation after SAH was very long-lasting and still present at day 21 as determined by Iba-1 staining (microglia/macrophages) and GFAP (astrocytes). Long-term neuroinflammation was strongly associated with the degree of severity of SAH. Cerebral damage to gray- and white-matter was visualized by immunohistochemistry for MAP2 and MBP at 21 days after SAH. Severe SAH induced significant gray- and white-matter damage. MAP2 loss at day 21 correlated significantly with the acute neurological score determined at 24 h post-SAH. Sensorimotor behavior, determined by the adhesive removal task and von Frey test, was affected after severe SAH at day 21. In conclusion, we are the first to show that SAH induces ongoing cortical inflammation. Moreover, SAH induces mainly cortical long-term brain damage, which is associated with long-term sensorimotor damage.

Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

“…27,28 In our study, we found histological changes 7 days after SAH, and comparison of corpus callosum thickness of both hemispheres indicated white matter thinning ipsilateral to the SAH induction site. Similar observations were reported recently in a rat model.…”

“…Similar observations were reported recently in a rat model. 27 One possible explanation for this lateralization effect may be the presence of a more pronounced vasospasm near the initial bleeding site. 29 Many studies have investigated the role of DC in traumatic brain injury 10,11 and malignant MCA infarction, 12,13 and the beneficial effects of DC in malignant MCA infarction have led to the recommendation of including DC in current treatment guidelines.…”

“…Similar observations were reported recently in a rat model. 27 One possible explanation for this lateralization effect may be the presence of a more pronounced vasospasm near the initial bleeding site. …”

Electroacupunctre improves motor impairment via inhibition of microglia-mediated neuroinflammation in the sensorimotor cortex after ischemic stroke

“…Long-term neuroinflammation is strongly induced gray-and white-matter damage, which contributes to long-term sensorimotor impairment [57]. Therefore, a therapeutic strategy for against the neuroinflammation is able to improve the neurological and sensorimotor deficits [58].…”

Rat Endovascular Perforation Model

“…Inflammation: Is studied as the activation of inflammatory molecules and cytokines 23, 24 . Inflammation is observed as adhesion of platelet aggregates and neutrophil to the walls of small cerebral vessels 25–27 and as increased immunoreactivity to nestin, ED1, OX6, intercellular adhesion molecule 1, and tumor necrosis factor 23 .…”