Experimental neurology
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Experimental neurology · Jan 2007
Comparative StudyBrain metabolism and extracellular space diffusion parameters during and after transient global hypoxia in the rat cortex.
Hypoxia results in both reversible and irreversible changes in the brain extracellular space (ECS). This study utilized microdialysis to monitor changes in the energy-related metabolites lactate, pyruvate, glucose and glutamate in the rat cortex before, during and after 30-min transient global hypoxia, induced in anesthetized rats by reducing inspired oxygen to 6% O(2) in nitrogen. Changes in metabolite levels were compared with ECS diffusion parameters calculated from diffusion curves of tetramethylammonium applied by iontophoresis. ⋯ Within 10 min of reoxygenation, alpha returned to control values, then increased to 0.20+/-0.01 and remained at this level until the end of the experiment. The observed 22% decrease in alpha markedly influences dialysate levels measured during hypoxia. In our study, the complete posthypoxic recovery of cortical metabolite levels and ECS diffusion properties suggests that metabolic enzymes and related cellular components (e.g., mitochondria) may tolerate prolonged hypoxic periods and recover to prehypoxic values.
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Experimental neurology · Jan 2007
Late effects of enriched environment (EE) plus multimodal early onset stimulation (MEOS) after traumatic brain injury in rats: Ongoing improvement of neuromotor function despite sustained volume of the CNS lesion.
Recently we showed that the combination between MEOS and EE applied to rats for 7-15 days after traumatic brain injury (TBI) was associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction. In a continuation of this work, we tested whether these effects persisted for longer post-operative periods, e.g. 30 days post-injury (dpi). Rats were subjected to lateral fluid percussion (LFP) or to sham injury. ⋯ We found (i) no differences in the vibrissal motor performance; (ii) EE+MEOS rats performed significantly better than SH rats in NS; (iii) EE-only and EE+MEOS animals, but not SH rats, showed better recovery at 30 dpi than at 15 dpi; (iv) no differences among all groups in CLV (larger than that at 15 dpi) and CLV-RAP, despite a clear tendency to reduction in the EE-only and EE+MEOS rats. We conclude that EE+MEOS retards, but cannot prevent the increase of lesion volume. This retardation is sufficient for a continuous restoration of neurological functions.
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Experimental neurology · Dec 2006
Comparative StudyThe effects of botulinum neurotoxin A induced muscle paresis during a critical period upon muscle and spinal cord development in the rat.
The second postnatal week is a critical period in rat motor development. The expansion of corticospinal innervation coincides with elimination of polyneuronal innervation of muscles, onset of quadrupedal locomotion and refinement of muscle afferent input to the ventral horn. Such developmental events are believed to be activity-dependent. ⋯ However, CTB labelling also revealed significantly increased motor axon terminals in the ventral Renshaw cell region in BTX-treated animals at P31, accompanied by raised expression of cJun in ipsilateral motoneurones. BTX-treated animals showed deficits in ladder walking, and their muscles contained a higher density and significantly more clustering of slow myosin expressing muscle fibres than controls. Temporary reduction in activity did not significantly alter muscle afferent development, but temporary blockade of neuromuscular junctions did affect both muscle and motor axon, in the longer term.
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Experimental neurology · Dec 2006
Comparative Study2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats.
2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and antiproapoptotic activities. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries might activate a unique signaling pathway, hypoxia-inducible factor-1alpha (HIF-1alpha), to produce or enhance cerebral vasospasm after subarachnoid hemorrhage (SAH). ⋯ Thick blood clot was observed around basilar artery under arachnoids in all animals except Sham group; severe morphological vasospasm was observed in basilar arteries in SAH and SAH+DMSO rats, and the mild vasospasm in rats treated with 2ME2 and D609; 2ME2 and D609 reduced the activity of HIF-1alpha in the basilar arteries by HIF-1alpha DuoSet ELISA; reduce the expression of HIF-1alpha, VEGF, BNIP3 and PCNA in basilar arteries by Western blotting and immunohistochemical staining. In addition, it decreased the mortality and improved the neurological deficits. In conclusion, 2ME2 is a powerful agent to reduce cerebral vasospasm by inhibiting HIF-1alpha activity and the expression of VEGF as its downstream, suppressing endothelium and VSMCs apoptosis via BNIP3 pathway, and attenuating vasoproliferation.
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Experimental neurology · Dec 2006
Comparative StudyBlocking EphA4 upregulation after spinal cord injury results in enhanced chronic pain.
Spinal cord injury (SCI) is characterized by a total or partial loss of motor and sensory functions due to the inability of neurons to regenerate. This lack of axonal regenerative response has been associated with the induction of inhibitory proteins for regeneration, such as the Eph receptor tyrosine kinases. One member of this family, the EphA4 receptor, coordinates appropriate corticospinal fibers projections during early development and is expressed in spinal commissural interneurons. ⋯ No locomotor recovery was observed in the rats treated with the EphA4-antisense ODN. Interestingly, reducing EphA4 expression increased mechanical allodynia, as observed by the Von Frey test and decreased exploratory locomotor activity. These results indicate that upregulation of EphA4 receptor after trauma may prevent the development of abnormal pain syndromes and could potentially be exploited as a preventive analgesic mediator to chronic neuropathic pain.