Our studies over the years have demonstrated that the eCB system has the ability to affect the functional outcome after TBI by a variety of mechanisms. The acute, neuroprotective effects are exerted by the eCB within hours and involve inhibition of excitatory neural transmission, inhibition of the inflammatory response and reducing vascular tone. The delayed, neuro-regenerative effects are probably mediated via proliferation of neural progenitor cells. This project aims to explore each of the eCB, CB-like and synthetic analogs that will be tested in-vivo, and proven to be effective in ameliorating the functional outcome after TBI, and which mechanism(s) is involved in affording its effect. Which receptor(s), enzyme(s) and/or signalling pathways are the targets of these molecules, and what sort of interaction with these targets are responsible for mediating the beneficial effect. We will be focusing on each of the multiple components of the neurovascular unit, namely, neurons, astrocytes (and microglia) and the cerebral vasculature, to identify the nature of their specific interaction with the eCB, which appears as a pan-protective system in the CNS, and in the whole body, in general. (For references see our review in Br J Pharmacol. (11) 163 1402–1410).
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- A. Cohen-Yeshurun, D.Willner, V. Trembovler, A. Alexandrovitch, R. Mechoulam, E. Shohami, R.R.Leker. N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury. J. Cereb Blood Flow Metab. 33, 1242-1250 (2013).
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