Brain research
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Hypoxic-ischemic injury in term neonates remains a significant cause of long-term neurological morbidity. The post-natal day 10 (P10) mouse is accepted as a model for the term human. This study was designed to assess the relationships between the duration of hypoxia-ischemia (HI) on P10 and the structural and functional neurological deficits that appear in the adult mouse as a consequence. ⋯ After correcting for motor deficits, there is evidence for persistence of "cued" learning but not spatial learning with increasing hypoxia-ischemia time on P10 in this model system.
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Clonidine, a specific alpha2-adrenergic receptor agonist, has been found to be effective for the treatment of neuropathic pain, the mechanism underlying the effect is, however, not well understood. Here, the effect of clonidine on long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn, which is a synaptic model of injury-induced hyperalgesia, was investigated. ⋯ We found that (1) Clonidine completely blocked LTP induction, when applied 30 min before tetanic stimulation and depressed spinal LTP, when applied 30 min and 3 h after LTP induction. (2) The inhibitory effect of clonidine on spinal LTP had two phases: a fast phase lasting for about 3.5 h and a slow phase persisting for the rest time of experiments (up to 8 h after drug). (3) Spinal clonidine at low dose (10.7 micro g/100 micro l) depressed spinal LTP but not C-fiber baseline response and at higher dose (107 micro g/100 micro l) depressed both of them. (4) Pretreatment with alpha2-adrenergic receptor antagonist yohimbine completely blocked the inhibitory effect of clonidine. (5) Pretreatment with muscarinic receptor antagonist atropine, nitric oxide synthesis inhibitor l-NNA or cGMP inhibitor ODQ depressed the fast phase inhibition significantly and abolished the slow phase inhibition completely. These results suggest that clonidine may exert analgesic effect by depressing the synaptic plasticity in spinal dorsal horn, via activation of muscarinic receptor-NO-cGMP pathway.