Experimental neurology
-
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.
-
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.
-
Experimental neurology · Dec 2008
Effects of combined dorsolateral and dorsal funicular lesions on sensorimotor behaviour in rats.
The purpose of this research was to investigate the compensatory role of undamaged spinal pathways after partial spinal injury in rats. We have previously shown that bilateral lesions of the dorsal funiculus (DF) at the cervical level caused changes in overground and skilled locomotion that affected the forelimbs more than the hindlimbs. The same lesions also caused fore-paw deficits during a skilled pellet retrieval task (Kanagal and Muir, 2007). ⋯ During both ladder crossing and reaching, secondary lesions to DF (with or without CST) exacerbated the deficits seen after initial DLF lesions and additionally caused changes in the manner in which the rats used their forelimbs during reaching. Nevertheless, the relative magnitude of the deficits indicates that DF pathways in rats likely do not compensate for loss of DLF pathways during the execution of locomotor tasks, though there is indirect evidence that DLF-lesioned rats might rely more on ascending sensory pathways in the DF during skilled forelimb movements. The plastic changes mediating recovery are therefore necessarily occurring in other regions of the CNS, and, importantly, need time to develop, because animals with DLF+DF lesions performed simultaneously displayed marked functional deficits and were unable to use their forelimbs for skilled locomotion or reaching.
-
Experimental neurology · Dec 2008
Diazepam delays the death of hippocampal CA1 neurons following global ischemia.
Although diazepam provides limited long term neuroprotection, it may be useful for expanding the therapeutic time window after stroke by delaying neuronal death. However, it is not known to what extent diazepam maintains normal cellular structure and function in the first few days after ischemia. We used histological, immunohistochemical and electrophysiological endpoints to address this question. ⋯ Most importantly, CA1 field potentials were similar to sham values and significantly preserved relative to non-treated ischemic gerbils. Diazepam maintains near normal structural and functional integrity up to 3 days after a global ischemic insult. As such, this drug may be useful for extending the therapeutic time window after cardiac arrest, stroke and related disorders.
-
Experimental neurology · Dec 2008
An integrin inhibiting molecule decreases oxidative damage and improves neurological function after spinal cord injury.
Our previous studies have shown that treatment with an alpha4beta1 integrin blocking antibody after spinal cord injury (SCI) in rats decreases intraspinal inflammation and oxidative damage, improving neurological function. Here, we studied effects of a high affinity small molecule alpha4beta1 inhibitor, BIO5192. First, rats were treated intravenously with BIO5192 (10 mg/kg) or with vehicle (controls) to assess effects of integrin blockade for 24 h or 72 h after thoracic clip-compression SCI. ⋯ BIO5192 treatment also decreased mechanical allodynia elicited from the trunk and hind paw by up to 35%. This improved function correlated with decreased lesion size and spared myelin-containing white matter. The neurological improvement offered by this neuroprotective strategy supports the potential for an anti-integrin treatment for SCI.