Abstract
Early brain injury (EBI) which comprises of vasogenic edema and apoptotic cell death is an important component of subarachnoid hemorrhage (SAH) pathophysiology. This study evaluated whether cannabinoid receptor type 2 (CB2R) agonist, JWH133, attenuates EBI after SAH and whether CB2R stimulation reduces pro-apoptotic caspase-3 via up-regulation of cAMP response element-binding protein (CREB)-Bcl-2 signaling pathway. Male Sprague-Dawley rats (n. = 123) were subjected to SAH by endovascular perforation. Rats received vehicle or JWH133 at 1. h after SAH. Neurological deficits and brain water content were evaluated at 24. h after SAH. Western blot was performed to quantify phosphorylated CREB (pCREB), Bcl-2, and cleaved caspase-3 levels. Neuronal cell death was evaluated with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. Additionally, CREB siRNA was administered to manipulate the proposed pathway. JWH133 (1.0. mg/kg) improved neurological deficits and reduced brain water content in left hemisphere 24. h after SAH. JWH133 significantly increased activated CREB (pCREB) and Bcl-2 levels and significantly decreased cleaved caspase-3 levels in left hemisphere 24. h after SAH. CREB siRNA reversed the effects of treatment. TUNEL positive neurons in the cortex were reduced with JWH133 treatment. Thus, CB2R stimulation attenuated EBI after SAH possibly through activation of pCREB-Bcl-2 pathway. © 2014 Elsevier Inc.
Original language | English |
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Pages (from-to) | 396-403 |
Number of pages | 8 |
Journal | Experimental Neurology |
Volume | 261 |
DOIs | |
State | Published - Nov 2014 |
ASJC Scopus Subject Areas
- Neurology
- Developmental Neuroscience
Keywords
- Apoptosis
- Brain edema
- CREB
- Cannabinoid receptor type 2
- JWH133
- Subarachnoid hemorrhage
- CREB-Binding Protein/metabolism
- Caspase 3/metabolism
- Cannabinoids/pharmacology
- Apoptosis/drug effects
- Rats
- Male
- Brain Injuries/etiology
- Rats, Sprague-Dawley
- Signal Transduction/drug effects
- Enzyme Inhibitors/pharmacology
- Receptor, Cannabinoid, CB2/agonists
- Subarachnoid Hemorrhage/complications
- Animals
- Time Factors
- Proto-Oncogene Proteins c-bcl-2/metabolism
- Disease Models, Animal
- Phosphorylation/drug effects