Diffuse microglial responses and persistent EEG changes correlate with poor neurological outcome in a model of subarachnoid hemorrhage.

The mechanism by which subarachnoid hemorrhage (SAH) leads to chronic neurologic deficits is unclear. One possibility is that blood activates microglia to drive inflammation that leads to synaptic loss and impaired brain function. Using the endovascular perforation model of SAH in rats, we investigated short-term effects on microglia together with long-term effects on EEG and neurologic function for up to 3 months. Within the first week, microglia were increased both at the site of injury and diffusely across the cortex (2.5-fold increase in SAH compared to controls, p = 0.012). Concomitantly, EEGs from SAH animals showed focal increases in slow wave activity and diffuse reduction in fast activity. When expressed as a fast-slow spectral ratio, there were significant interactions between group and time (p < 0.001) with less ipsilateral recovery over time. EEG changes were most pronounced during the first week and correlated with neurobehavioral impairment. In vitro, the blood product hemin was sufficient to increase microglia phagocytosis nearly six-fold (p = 0.032). Immunomodulatory treatment with fingolimod after SAH reduced microglia, improved neurological function, and increased survival. These findings, which parallel many of the EEG changes seen in patients, suggest that targeting neuroinflammation could reduce long-term neurologic dysfunction following SAH.

Systemic Immune-Inflammation Index Predicts Delayed Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS: We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS: A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P < .001). In univariate logistic regression, leukocytes, neutrophils, lymphocytes, neutrophil-lymphocyte ratio (NLR), and SII index were associated with vasospasm. After adjustment for age, aneurysm location, diabetes mellitus, hyperlipidemia, and modified Fisher scale, SII index remained an independent predictor of vasospasm (odds ratio 1.386, P = .003). ROC analysis revealed that SII index accurately distinguished between patients who develop vasospasm vs those who do not (area under the curve = 0.767, P < .001). CONCLUSION: Early elevation in SII index can independently predict the development of delayed cerebral vasospasm in aneurysmal SAH.