The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies

Abstract

Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed.SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH.Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult.

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

“…Moreover, the sympathetic pathway has been reported in multiple experimental studies to be the communication link between the neural and immune systems [15, 25]. Numerous clinical studies have even reported that stroke patients with high NA levels are at increased risk of SAI [16–17].…”

New Grading System Based on Magnetic Resonance Imaging in a Mouse Model of Subarachnoid Hemorrhage

“…1 The endovascular perforation method for inducing SAH is frequently used in rodents, and is considered to the closest imitation of human SAH. 2,3 In that model, there are greater inter-animals variations in the extent and volume of subarachnoid clot compared to other SAH models. 4 A method established by Sugawara et al 5 is commonly used to evaluate the SAH severity in perforation models of rodent SAH, but this is performed after euthanasia by visualizing clot extension and thickness at the base of the brain.…”

Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: Possible involvement of TLR4/NF-κB-mediated inflammatory pathway

“…Therefore, EBI has emerged as a new frontier and requires a better understanding and consideration in devising therapeutic strategy for improving SAH outcomes. The pathophysiological mechanisms of EBI are complicated and increasing evidences suggest that inflammatory mechanisms are involved in the progression of EBI after SAH (Cahill et al, 2006;Kooijman et al, 2014;Sehba et al, 2012). Following SAH, glial cells are activated (Kooijman et al, 2014), BBB permeability is increased (Cahill et al, 2006) and peripheral immune cells infiltrate into the brain (Sehba et al, 2012), leading to the production of a great number of inflammatory cytokines and chemokines, which induce brain edema and neuronal injury.…”