Strokes

Archive for the ‘Strokes’ Category

Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia. [Comparative Study, Journal Article, Research Support, Non-U.S. Gov't]

June 18th, 2010 | Author: Brett

Delta(9)-tetrahydrocannabinol (Delta(9)-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB(1) receptor. In this study, Delta(9)-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Delta(9)-THC was completely abolished by SR141716, cannabinoid CB(1) receptor antagonist, and by warming the animals to 31 degrees C. Delta(9)-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 degrees C. At 24 h after cerebral ischemia, Delta(9)-THC significantly increased the expression level of CB(1) receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 degrees C during 4 h cerebral ischemia did not increase the expression of CB(1) receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Delta(9)-THC is mediated by a temperature-dependent mechanism via the CB(1) receptor. In addition, warming to 31 degrees C might attenuate both the neuroprotective and hypothermic effects of Delta(9)-THC through inhibiting the increase in CB(1) receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Delta(9)-THC.

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Cannabinoid CB2 receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model

June 18th, 2010 | Author: Brett

Cannabinoid CB₂ Receptor (CB₂) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB₂ agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB₂ agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB₂ agonists significantly decreased cerebral infarction (30%) and improved motor function (P < 0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P < 0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB₂ agonists administered either at 1 h before or after MCAO (P < 0.05). CB₂ activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.

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Δ9-Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors

June 18th, 2010 | Author: Brett

Background and purpose:

It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage. In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB₁) agonist, Δ⁹-tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil.

Experimental approach:

The effects of AM 404 (0.015–2

Δ9 Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors

kg⁻¹) and THC (0.05–2

kg⁻¹), given 5

min after ischaemia, were measured from 1

h to 7 days in terms of electroencephalographic (EEG) total spectral power, spontaneous motor activity, memory function, rectal temperature and hippocampal CA₁ neuronal count.

Key results:

Over the dose range tested, AM 404 (2

kg⁻¹) and THC (1

kg⁻¹) completely reversed the ischaemia-induced behavioural, EEG and histological damage. Only THC (1 and 2

kg⁻¹) induced a decrease of body temperature. Pretreatment with the selective CB₁ receptor antagonist, AM 251 (1

kg⁻¹) and the opioid antagonist, naloxone (2

kg⁻¹) reversed the protective effect induced by both AM 404 and THC while the TRPV₁ vanilloid antagonist, capsazepine (0.01

kg⁻¹), was ineffective.

Conclusions and implications:

Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB₁ and opioid receptors. Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.

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Role of cannabinoids and endocannabinoids in cerebral ischemia

June 18th, 2010 | Author: Brett

The human costs of stroke are very large and growing; it is the third largest cause of death in the United States and survivors are often faced with loss of ability to function independently. There is a large need for therapeutic approaches that act to protect neurons from the injury produced by ischemia and reperfusion. The goal of this review is to introduce and discuss the available data that endogenous cannabinoid signaling is altered during ischemia and that it contributes to the consequences of ischemia-induced injury. Overall, the available data suggest that inhibition of CB1 receptor activation together with increased CB2 receptor activation produces beneficial effects.

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