Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V
max (complexes I, III, and IV activities), V
succ (complexes II, III, and IV activities), V
tmpd (complex IV activity), together with mitochondrial coupling (V
max/V
0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2) production, measured with Amplex Red. THC significantly decreased V
max (−71%; P < 0.0001), V
succ (−65%; P < 0.0001), and V
tmpd (−3.5%; P < 0.001). Mitochondrial coupling (V
max/V
0) was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P < 0.001). Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P < 0.05) and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P < 0.001). Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient's vulnerability to stroke.
This study compares a vigorous shaking and an inflicted impact, defined as the terminal portion of a vigorous shaking, using a finite element model of a 6-month-old child head. Whereas the calculated values in terms of shearing stress and brain pressure remain different and corroborate the previous studies based on angular and linear velocity and acceleration, the calculated relative brain and skull motions that can be considered at the origin of a subdural haematoma show similar results for the two simulated events. Finite element methods appear as an emerging tool in the study of the biomechanics of head injuries in children.
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