Experimental neurology
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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.
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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
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 · Dec 2007
Changes in immunoreactivity of HSP60 and its neuroprotective effects in the gerbil hippocampal CA1 region induced by transient ischemia.
Heat shock proteins act as molecular chaperones and are involved in protein folding, refolding, transport, and translocation. In the present study, we observed changes in heat shock protein 60 (HSP60) immunoreactivity and protein level in the gerbil hippocampal CA1 region after 5 min of transient forebrain ischemia and its neuroprotective effect against ischemic damage. HSP60 immunoreactivity in the CA1 region began to increase in the stratum pyramidale at 30 min after ischemia/reperfusion, and peaked 24 h after ischemia/reperfusion. ⋯ In Western blot study, HSP60 protein level in the CA1 region was increased after ischemia/reperfusion and highest 24 h after ischemia/reperfusion. Animals treated with recombinant adenoviruses expressing Hsp60 (Ad-Hsp60) showed the neuroprotection of CA1 pyramidal neurons from ischemic damage. These results suggest that HSP60 may be associated with delayed neuronal death of CA1 pyramidal neurons after transient ischemia, and the induction of HSP60 protects the neurons from ischemic damage.
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Experimental neurology · Dec 2007
Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain.
Our previous study has reported that electroacupuncture (EA) at low frequency of 2 Hz had greater and more prolonged analgesic effects on mechanical allodynia and thermal hyperalgesia than that EA at high frequency of 100 Hz in rats with neuropathic pain. However, how EA at different frequencies produces distinct analgesic effects on neuropathic pain is unclear. Neuronal plastic changes in spinal cord might contribute to the development and maintenance of neuropathic pain. ⋯ Results from our present study suggest that (1) hyperexcitability in the spinal nociceptive synaptic transmission may occur after nerve injury, which may contribute to the development of neuropathic pain; (2) EA at low or high frequency has a different effect on modulating spinal synaptic plasticities in rats with neuropathic pain. The different modulation on spinal LTD or LTP by low- or high-frequency EA may be a potential mechanism of different analgesic effects of EA on neuropathic pain. LTD of synaptic strength in the spinal dorsal horn in SNL rats may contribute to the long-lasting analgesic effects of EA at 2 Hz.