Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rapid and reproducible spinal motor neuron death occurs after sciatic nerve transection in neonatal rats. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors, such as ciliary neurotrophic factor, brain-derived neurotrophic factor, leukemia inhibitory factor and glial cell line-derived neurotrophic factor. Another hypothesis suggests that glutamate and its receptors has been implicated as possible mechanism for motor neuron death. In order to investigate the effect of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on axotomy-induced cell death in the spinal motor neurons of neonatal rats, we have studied neuroprotective effects of these receptor antagonists. Newborn rats were anesthetized with hypothermia. Sciatic nerve was transected near the obturator tendon in the left thigh. Animals were then treated daily with MK-801, APV, and CNQX for 14 days with intraperitoneal injections. Control animals received PBS in the same fashion. After the treatment, the number of spinal motor neurons in the L4-6 was counted. MK-801 and APV did not show any significant neuroprotective effect. By contrast, the number of surviving motor neurons was greater in animals that were treated with 1.0, 2.0 and 4.0 mg/kg of CNQX. This neuroprotective effect was not dose-related. We demonstrate that neuroprotective effect of CNQX on axotomized motor neurons, raises a possibility that such a agent may have therapeutic potential in motor neuronopathy and amyotrophic lateral sclerosis.
 ...
PMID:CNQX prevents spinal motor neuron death following sciatic nerve transection in newborn rats. 874 38

Hypothermia has been reported to be beneficial in CNS physical injury and ischemia. We previously reported that posttraumatic cooling to 17 degrees C for 2 h increased survival of mouse spinal cord (SC) neurons subjected to physical injury (dendrite transection) but that cooling below 17 degrees C caused a lethal NMDA receptor-linked stress to both lesioned and uninjured neurons. The present study tested whether cooling below 17 degrees C increases extracellular levels of excitatory amino acids (EAA). SC cultures were placed at 10 degrees C or 37 degrees C. Glutamate (Glu) and aspartate (Asp) levels were higher in the medium of the cooled cultures after 0.5 h (23 +/- 4 nM/microgram vs. 4 +/- 1 nM/microgram and 4 +/- 1 nM/microgram vs. 1 +/- 0 nM/microgram, respectively). The concentration of each EAA then declined and reached a plateau at 2-4 h that was still significantly higher than control levels (p < 0.0001, two-factor ANOVA, three cultures per group). Other amino acids (glycine, asparagine, glutamine, serine) showed an opposite pattern, with higher levels in the 37 degrees C group. Both NMDA and non-NMDA antagonists prevented the lethal cold injury. Survival of SC neurons cooled at 10 degrees C for 2 h and rewarmed for 22 h was 58% +/- 25% in the control group, 94% +/- 5% in the CNQX-treated group, 97% +/- 5% in the DAPV-treated group, and 99% +/- 2% in the group treated with both antagonists [p < 0.0006, one factor ANOVA, five cultures (> 120 neurons) per group]. These results show that death of neurons cooled to 10 degrees C is caused by elevated extracellular Glu and Asp and requires activation of both the NMDA and non-NMDA receptor subtypes.
 ...
PMID:The role of excitatory amino acids in hypothermic injury to mammalian spinal cord neurons. 900 66

Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31 degrees C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (omega-conotoxin MVIIC, 3 microM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 microM; lidocaine, 200 microM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 microM; the non-NMDA receptor antagonist CNQX, 10 microM/100 microM glycine; the NMDA receptor antagonist CCP, 100 microM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.
 ...
PMID:Intraneuronal ion distribution during experimental oxygen/glucose deprivation. Routes of ion flux as targets of neuroprotective strategies. 1066 26