Experimental neurology
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Experimental neurology · Jan 2009
Impaired dendritic development and synaptic formation of postnatal-born dentate gyrus granular neurons in the absence of brain-derived neurotrophic factor signaling.
Neurons are continuously added to the hippocampal dentate gyrus throughout life. These neurons must develop dendritic arbors and spines by which they form synapses for making functional connections with existing neurons. The molecular mechanisms that regulate dendritic development and synaptic formation of postnatal-born granular neurons in the dentate gyrus are largely unknown. ⋯ Even though, these BDNF-deficient granular neurons develop immature dendritic spines to initiate synaptic contacts with afferent axons, they fail to develop or maintain mature spine structures. Thus, these postnatal-born neurons have fewer numbers of synapses, particularly mature synaptic spines. These results suggest that BDNF plays an important role during dendritic development, synaptic formation and synaptic maturation in postnatal-born granular neurons of the HDG in vivo.
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Experimental neurology · Jan 2009
Genetic inactivation of adenosine A2A receptors attenuates acute traumatic brain injury in the mouse cortical impact model.
The inactivation of the A(2A) receptor (A(2A)R) has been shown to neuroprotect against brain injury in several animal models of neurological disorders including stroke and Parkinson's disease. However, despite marked elevation of adenosine level, the role of the A(2A) in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the effects of genetic inactivation of A(2A)Rs in the acute stage. ⋯ In addition, we found that at 12 h post-TBI the mRNA and protein levels of TNF-alpha and IL-1beta were higher in the KO mice than that in the WT littermates. However, at 24 h post-TBI, the level of TNF-alpha and IL-1beta continually increased in the WT mice but largely declined in the KO mice. These results suggest that the genetic inactivation of A(2A)R protects against TBI, which is mainly associated with the suppression of glutamate level.
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Experimental neurology · Jan 2009
Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats.
In the present study, cerebral ischemia was induced by a 10 min transient bilateral common carotid artery occlusion in rats combined with arterial blood pressure lowering to 37-42 mm Hg during occlusion. When histologically evaluated at 7 and 28 days after the forebrain ischemia (DAI) by staining with cresyl violet and Fluoro-Jade, the hippocampal CA1 region was most prominently damaged. At 7 DAI, treatment with cilostazol (60 mg/kg/day, orally) significantly reduced the neuronal damage in the CA1 region. ⋯ To elucidate whether cilostazol enhances hippocampal neurogenesis after ischemia, we planned a co-labeling study using 5-bromo-2'-deoxyuridine (BrdU), NeuN (a marker for mature neurons) and doublecortin (DCX) (a marker for immature migratory neuroblasts). Double immunofluorescence staining at 7 DAI showed that cilostazol significantly increased the immunoreactivities of both DCX and phosphorylated cAMP-response element-binding protein (CREB) in the dentate gyrus that was co-expressed with BrdU. These results suggest that cilostazol has dual beneficial effects preserving the CA1 hippocampal region and promoting the generation of immature migratory neuroblasts in the dentate gyrus by upregulation of CREB phosphorylation after transient forebrain ischemia.
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Experimental neurology · Dec 2008
Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.
The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. ⋯ In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.
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Experimental neurology · Dec 2008
Modulation of paratrigeminal nociceptive neurons following temporomandibular joint inflammation in rats.
To evaluate the involvement of paratrigeminal nucleus (Pa5) nociceptive neurons in temporomandibular joint (TMJ) inflammation-induced pain and its autonomic correlates, we conducted behavioral, single unit recording and Fos immunohistochemical studies in anesthetized rats. Nocifensive behaviors to mechanical, heat or cold stimulation of the lateral face over the TMJ region were significantly enhanced in the TMJ-inflamed rats for 10-14 days after injection of complete Freund's adjuvant (CFA) into the TMJ and gradually decreased at the end of the 14-day observation period. Lowering of the nocifensive threshold in TMJ-inflamed rats lasted longer in vagus nerve-transected rats than vagus nerve-intact rats. ⋯ All thermal responsive Pa5 neurons were exclusively sensitive to cold and the response to cold was significantly higher in the TMJ-inflamed rats compared with control rats. Vagus nerve stimulation significantly decreased responses to mechanical and cold stimuli as well as the background activity in TMJ-treated rats but not in TMJ-untreated rats. The present findings suggest that populations of Pa5 neurons are nociceptive and involved in TMJ inflammation-induced pain as well as in autonomic processes related to TMJ pain.