New endovascular perforation subarachnoid hemorrhage model for investigating the mechanisms of delayed brain injury

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Kosuke Kumagai ◽  
Arata Tomiyama ◽  
Satoru Takeuchi ◽  
Naoki Otani ◽  
Masanori Fujita ◽  
...  

OBJECTIVEDelayed brain injury (DBI) is considered one of the most important causes of mortality and morbidity after subarachnoid hemorrhage (SAH). However, no suitable experimental rat endovascular perforation (EVP) SAH model was available for investigating DBI. The authors added early cerebral hypoperfusion to a mild EVP SAH model by unilateral common carotid artery occlusion (UCCAO) 24 hours after induction of SAH to mimic the clinical course of early cerebral hypoperfusion after SAH.METHODSA total of 109 adult male Sprague-Dawley rats were randomly divided into 2 groups: no SAH and SAH. Next, no-SAH rats were randomly divided on day 1 into 2 groups: sham and UCCAO. SAH rats with a neurological score of 15 or greater were randomly divided into 2 groups: SAH − UCCAO and SAH + UCCAO group.RESULTSThe mild SAH model had a lower mortality rate of 5.4% within the first 24 hours. No rat died in the SAH + UCCAO group until day 7. DBI as well as early brain injury (EBI), reactive astrogliosis, and cerebral vasospasm significantly worsened in the SAH + UCCAO group.CONCLUSIONSThe present SAH + UCCAO model can simulate EBI with aggravation of reactive astrogliosis, cerebral vasospasm, and DBI but without high mortality.

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Sabri ◽  
Elliot Lass ◽  
R. Loch Macdonald

Early brain injury (EBI) has become an area of extreme interest in the recent years and seems to be a common denominator in the pathophysiology of global transient ischemia and subarachnoid hemorrhage (SAH). In this paper, we highlight the importance of cerebral hypoperfusion and other mechanisms that occur in tandem in both pathologies and underline their possible roles in triggering brain injury after hemorrhagic or ischemic strokes.


2019 ◽  
Vol 34 (6) ◽  
pp. 1737-1746 ◽  
Author(s):  
Bora Gürer ◽  
Hayri Kertmen ◽  
Pınar Kuru Bektaşoğlu ◽  
Özden Çağlar Öztürk ◽  
Hüseyin Bozkurt ◽  
...  

2017 ◽  
Vol 130 ◽  
pp. 18-26 ◽  
Author(s):  
Tomoko Mutoh ◽  
Tatsushi Mutoh ◽  
Kazuhiro Nakamura ◽  
Kazumasu Sasaki ◽  
Yasuko Tatewaki ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 980 ◽  
Author(s):  
Chengmei Sun ◽  
Budbazar Enkhjargal ◽  
Cesar Reis ◽  
Tongyu Zhang ◽  
Qiquan Zhu ◽  
...  

Osteopontin (OPN) enhances autophagy, reduces apoptosis, and attenuates early brain injury (EBI) after a subarachnoid hemorrhage (SAH). A total of 87 Sprague–Dawley rats were subjected to sham or SAH operations to further investigate the signaling pathway involved in osteopontin-enhanced autophagy during EBI, and the potential effect of recombinant OPN (rOPN) administration to improve long-term outcomes after SAH. Rats were randomly divided into five groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), SAH + rOPN (5 μg/rat recombinant OPN), SAH + rOPN + Fib-14 (30 mg/kg of focal adhesion kinase (FAK) inhibitor-14), and SAH + rOPN + DMSO (dimethyl sulfoxide). Short-term and long-term neurobehavior tests were performed, followed by a collection of brain samples for assessment of autophagy markers in neurons, pathway proteins expression, and delayed hippocampal injury. Western blot, double immunofluorescence staining, Nissl staining, and Fluoro-Jade C staining assay were used. Results showed that rOPN administration increased autophagy in neurons and improved neurobehavior in a rat model of SAH. With the administration of FAK inhibitor-14 (Fib-14), neurobehavioral improvement and autophagy enhancement induced by rOPN were abolished, and there were consistent changes in the phosphorylation level of ERK1/2. In addition, early administration of rOPN in rat SAH models improved long-term neurobehavior results, possibly by alleviating hippocampal injury. These results suggest that FAK–ERK signaling may be involved in OPN-enhanced autophagy in the EBI phase after SAH. Early administration of rOPN may be a preventive and therapeutic strategy against delayed brain injury after SAH.


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