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Canna~Fangled Abstracts

Endocannabinoid degradation inhibition improves neurobehavioral function, blood brain barrier integrity, and neuroinflammation following mild traumatic brain injury.

By August 28, 2014No Comments
2014 Aug 28. [Epub ahead of print]

pm1Endocannabinoid degradation inhibition improves neurobehavioral function, blood brain barrier integrity, and neuroinflammation following mild traumatic brain injury.

Katz PS1, Sulzer JK, Impastato RA, Teng SX, Rogers EK, Molina P.

Author information

Abstract

Traumatic brain injury (TBI) is an increasingly frequent and poorly understood condition lacking effective therapeutic strategies. Inflammation and oxidative stress are critical components of injury and targeted interventions to reduce their contribution to injury should improve neurobehavioral recovery and outcomes. Recent evidence reveals potential protective, yet short-lived effects of the endocannabinoids (ECs), 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA), on neuroinflammatory and oxidative stress processes following TBI. The aim of this study was to determine if EC degradation inhibition following TBI would improve neurobehavioral recovery by reducing inflammatory and oxidative damage. Adult male Sprague-Dawley rats underwent a 5mm left lateral craniotomy and TBI was induced by lateral fluid percussion. TBI produced apnea (17±5 sec) and a delayed righting reflex (479±21 sec). Thirty minutes post-TBI, rats were randomized to receive intraperitoneal injections of vehicle (alcohol, emulphor, and saline; 1:1:18), or a selective inhibitor of 2-AG (JZL184, 16mg/kg) or AEA (URB597, 0.3mg/kg) degradation. At 24 hrs post-TBI animals showed significant neurological and neurobehavioral impairment, and disruption of blood brain barrier (BBB) integrity. Improved neurological and neurobehavioral function was observed in JZL 184-treated animals. BBB integrity was protected in both JZL 184- and URB597-treated animals. No significant differences in ipsilateral cortex mRNA expression of IL-1β, IL-6, CCL2, TNF-, COX2 or NOX2, and protein expression of COX2 or NOX2 were observed across experimental groups. Astrocyte and microglia activation was significantly increased post-TBI and treatment with JZL 184 or URB597 blocked activation of both cell types. These findings suggest that EC degradation inhibition post-TBI exerts neuroprotective effects. Whether repeated dosing would achieve greater protection remains to be examined.

KEYWORDS:

BEHAVIORAL ASSESSMENTS; BLOOD-BRAIN BARRIER DYSFUNCTION; GLIA CELL RESPONSE TO INJURY; INFLAMMATION; TRAUMATIC BRAIN INJURY

PMID:

 25166905
[PubMed – as supplied by publisher]twin memes II