Experimental neurology
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Experimental neurology · Jan 2008
Brain metabolism and diffusion in the rat cerebral cortex during pilocarpine-induced status epilepticus.
The real-time iontophoretic method using tetramethylammonium-selective microelectrodes and diffusion-weighted magnetic resonance imaging were used to measure the extracellular space volume fraction alpha, tortuosity lambda and apparent diffusion coefficient of water (ADC(W)) 240 min after the administration of pilocarpine in urethane-anaesthetized rats. The obtained data were correlated with extracellular lactate, glucose, and glutamate concentrations and the lactate/pyruvate-ratio, determined by intracerebral microdialysis. The control values of alpha and lambda were 0.19+/-0.004 and 1.58+/-0.01, respectively. ⋯ Pilocarpine application led to a rise in lactate, the lactate/pyruvate ratio and glutamate levels, reaching 2.92+/-0.60 mmol/l, 84.80+/-11.72 and 22.39+/-5.85 micromol/l within about 100 min, with a subsequent decrease to control values 140 min later. The time course of changes in glucose levels was different, with maximal levels of 3.49+/-0.24 mmol/l reached 40 min after pilocarpine injection and a subsequent decrease to 1.25+/-0.40 mmol/l observed 200 min later. Pathologically increased neuronal activity induced by pilocarpine causes cell swelling followed by a reduction in the ECS volume fraction, which can contribute to the accumulation of toxic metabolites and lead to the start of epileptic discharges.
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Experimental neurology · Jan 2008
Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog.
Following traumatic brain injury (TBI), mitochondrial function becomes compromised. Mitochondrial dysfunction is characterized by intra-mitochondrial Ca(2+) accumulation, induction of oxidative damage, and mitochondrial permeability transition (mPT). Experimental studies show that cyclosporin A (CsA) inhibits mPT. ⋯ Treatment of animals with either NIM811 or CsA significantly (p<0.03) attenuated this reduction. Consistent with this finding, both NIM811 and CsA significantly reduced lipid peroxidative and protein nitrative damage to mitochondria at 12 h post-TBI. These results showing the ability of NIM811 to fully duplicate the mitochondrial protective efficacy of CsA supports the conclusion that inhibition of the mPT may be sufficient to explain CsA's protective effects.
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Experimental neurology · Jan 2008
Reorganization of sensory processing below the level of spinal cord injury as revealed by fMRI.
The adult mammalian CNS undergoes plastic changes in response to injury. To investigate such changes in spinal cord, functional magnetic resonance imaging (fMRI) was applied in rats subjected to complete transection of the mid-thoracic spinal cord. Blood oxygenation level-dependent (BOLD) contrasts were recorded in the distal spinal cord different times after injury (3, 7, and 14 days, and 1, 3, and 6 months) in response to electrical hind limb stimulation. ⋯ Reorganization in the injured spinal cord has been shown to involve the amplification of peripheral inputs and implicated as one underlying mechanism causing neuropathic pain and autonomic dysreflexia. Since BOLD signals can demonstrate such plastic changes in spinal cord parenchyma, we propose fMRI as a method to monitor functional reorganization in the spinal cord after injury. Combining brain and spinal cord fMRI allows the visualization of neuronal activities along the entire neuroaxis and thereby an evaluation of the different plastic responses to CNS injuries that occur in the brain and the spinal cord.