CB2 AGONIST IMPROVES MOTOR ACTIVITY AND REDUCES TISSUE DAMAGE AFTER CEREBRAL ISCHEMIA

LAURA CALTANA, DELIA SORIANO, FLORENCIA CONDE, MARINA VACOTTO, ALICIA BRUSCO.

Mar del Plata

Congreso; XXX CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2015

Sociedad Argentina de Investigación en Neurociencias

The cannabinoid receptor type 1 (CB1R) is expressed in neurons and glial cells in many brain regions, where they play neuromodulatory roles in synaptic transmission, while cannabinoid receptor type 2 (CB2R) is mainly expressed by cells of the immune system. Cannabinoids can exert anti-inflammatory effects by inhibiting the proliferation of lymphocytes and inducing their death by apoptosis.The aim of this work is to evaluate the potential neuroprotective effects of CB2R agonist treatment in a mouse model of middle cerebral artery occlusion (MCAo).We evaluated the effect of CB2R agonist (JWH015) and antagonist (AM630) in C57Bl/6 mice subjected to focal brain ischemia by MCAo. 3, 24 and 48 hours after MCAo, mice received JWH015 4mg/kg, AM630 1mg/kg. To assess motor activity, neural deficit score and motor tests were performed 1 day before and 3 and 7 after MCAo. At 7 days (D7) post- lesion, mice were fixed and their brains processed for immunohistochemistry for GFAP, MAP-2 and lectin. JWH015 reduced infarct area, neuronal dendrite loss, astroglial hypertrophy and hyperplasia. In contrast, AM630 increased these parameters of damage. Motor test data analyzed showed a progressive deterioration to D7 in ischemic animals and the CB2R agonist treatment produces an improvement in motor activity.The results suggest that CB2R agonists may be involved in neuronal survival and the regulation of neuroprotection during focal cerebral ischemia in mice by reducing inflammatory response.