Aneurysmal subarachnoid hemorrhage (aSAH) remains a disease with high mortality and morbidity. Since treating vasospasm has not inevitably led to an improvement in outcome, the actual emphasis is on finding neuroprotective therapies in the early phase following aSAH to prevent secondary brain injury in the later phase of disease. Within the early phase, neuroinflammation, thromboinflammation, disturbances in brain metabolism and early neuroprotective therapies directed against delayed cerebral ischemia (DCI) came into focus. Herein, the role of neuroinflammation, thromboinflammation and metabolism in aSAH is depicted. Potential neuroprotective strategies regarding neuroinflammation target microglia activation, metalloproteases, autophagy and the pathway via Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1), NF-κB and finally the release of cytokines like TNFα or IL-1. Following the link to thromboinflammation, potential neuroprotective therapies try to target microthrombus formation, platelets and platelet receptors as well as clot clearance and immune cell infiltration. Potential neuroprotective strategies regarding metabolism try to re-balance the mismatch of energy need and supply following aSAH, for example, in restoring fuel to the TCA cycle or bypassing distinct energy pathways. Overall, this review addresses current neuroprotective strategies in aSAH, hopefully leading to future translational therapy options to prevent secondary brain injury.

Object: Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism. Methods: Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (n = 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 minutes before until 3 hours after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA. Results: PDH activity was significantly reduced in animals subjected to SAH compared to controls. Conclusion: The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization and secondary brain damage.

Little is known about changes in brain metabolism following SAH, possibly leading towards secondary brain damage. Despite sustained progress in the last decade, analysis of in vivo acquired data still remains challenging. The present interdisciplinary study uses a semi-automated data analysis tool analyzing imaging data independently from the administrated radiotracer. The uptake of 2-[¹⁸F]Fluoro-2-deoxy-glucose ([¹⁸F]FDG) was evaluated in different brain regions in 14 male Sprague–Dawley rats, randomized into two groups: (1) SAH induced by the endovascular filament model and (2) sham operated controls. Serial [¹⁸F]FDG-PET measurements were carried out. Quantitative image analysis was performed by uptake ratio using a self-developed MRI-template based data analysis tool. SAH animals showed significantly higher [¹⁸F]FDG accumulation in gray matter, neocortex and olfactory system as compared to animals of the sham group, while white matter and basal forebrain region showed significant reduced tracer accumulation in SAH animals. All significant metabolic changes were visualized from 3 h, over 24 h (day 1), day 4 and day 7 following SAH/sham operation. This [¹⁸F]FDG-PET study provides important insights into glucose metabolism alterations following SAH—for the first time in different brain regions and up to day 7 during course of disease.