Neurotoxicity research
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Neurotoxicity research · Apr 2012
Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury.
Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. ⋯ Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.
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Neurotoxicity research · Feb 2012
Exercise pre-conditioning reduces brain inflammation and protects against toxicity induced by traumatic brain injury: behavioral and neurochemical approach.
Although the favorable effects of physical exercise in neurorehabilitation after traumatic brain injury (TBI) are well known, detailed pathologic and functional alterations exerted by previous physical exercise on post-traumatic cerebral inflammation have been limited. In the present study, it is showed that fluid percussion brain injury (FPI) induced motor function impairment, followed by increased plasma fluorescein extravasation and cerebral inflammation characterized by interleukin-1β, tumor necrosis factor-α (TNF-α) increase, and decreased IL-10. In addition, myeloperoxidase (MPO) increase and Na⁺,K⁺-ATPase activity inhibition after FPI suggest that the opening of blood-brain barrier (BBB) followed by neurtrophils infiltration and cerebral inflammation may contribute to the failure of selected targets leading to secondary damage. ⋯ This protocol of physical training was effective against MPO activity increase and Na⁺,K⁺-ATPase activity inhibition after FPI. The present protection correlated with MPO activity decrease suggests that the alteration of cerebral inflammatory status profile elicited by previous physical training reduces initial damage and limits long-term secondary degeneration after TBI. This prophylactic effect may facilitate functional recovery in patients suffering from brain injury induced by TBI.
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Neurotoxicity research · Jan 2012
Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) are more susceptible to retinal ischemic injury in vivo.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective peptide exerting protective effects in neuronal injuries. We have provided evidence that PACAP is neuroprotective in several models of retinal degeneration in vivo. Our previous studies showed that PACAP treatment ameliorated the damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid artery occlusion. ⋯ It was found that PACAP deficient mice had significantly greater retinal damage, as shown by the thickness of the whole retina, the morphometric analysis of the individual retinal layers, and the cell numbers in the inner nuclear and ganglion cell layers. Exogenous PACAP administration could partially protect against retinal degeneration in PACAP deficient mice. These results clearly show that endogenous PACAP reacts as a stress-response peptide that is necessary for endogenous protection against different retinal insults.
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Neurotoxicity research · Nov 2011
Co-administration of cisplatin and furosemide causes rapid and massive loss of cochlear hair cells in mice.
The expanding arsenal of transgenic mice has created a powerful tool for investigating the biological mechanisms involved in ototoxicity. However, cisplatin ototoxicity is difficult to investigate in mice because of their small size and vulnerability to death by nephrotoxicity. To overcome this problem, we developed a strategy for promoting cisplatin-induced ototoxicity by coadministration of furosemide a loop diuretic. ⋯ Combined treatment with 0.5 mg/kg of cisplatin and 200 mg/kg furosemide resulted in only moderate loss of outer hair cells in the basal 20% of the cochlea, only mild threshold shifts and minimal loss of distortion product otoacoustic emission (DPOAE). In contrast, 1 mg/kg of cisplatin plus 200 mg/kg of furosemide resulted in a permanent 40-50 dB elevation of auditory brainstem response thresholds, almost complete elimination of DPOAE, and nearly total loss of outer hair cells. The widespread outer hair cell lesions that develop in mice treated with cisplatin plus furosemide could serve as extremely useful murine model for investigating techniques for regenerating outer hair cells, studying the mechanisms of cisplatin and furosemide ototoxicity and assessing the perceptual and electrophysiological consequences of outer hair cell loss on central auditory plasticity.
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Neurotoxicity research · Aug 2011
Extracellular HMGB1 released by NMDA treatment confers neuronal apoptosis via RAGE-p38 MAPK/ERK signaling pathway.
High mobility group box 1 (HMGB1) was originally identified as ubiquitously expressed nonhistone DNA-binding protein, but recently, it was found to act as an endogenous danger molecule, which signals danger and traumatic cell death. Previously, the authors showed that HMGB1 is massively released immediately after an ischemic insult and that it subsequently activates microglia and induces inflammation in the postischemic brain. Here, we showed the endogenous danger molecule-like function of HMGB1 in primary cortical cultures. ⋯ It was interesting to find that extracellular HMGB1-induced neuronal apoptosis, as evidenced by TUNEL staining and caspase 3 assay in combination with double immunofluorescence staining. A series of RAGE and HMGB1 co-immunoprecipitation experiments in the presence of SB203580 and PD98059 (p38 MAPK and ERK inhibitors, respectively) demonstrated that RAGE-p38 MAPK and RAGE-ERK pathway might underlie extracellular HMGB1-mediated neuronal apoptosis. These results together with our previous reports regarding microglial activation by extracellular HMGB1 indicate that HMGB1 functions as a novel danger signal, which aggravates brain damage via autocrine and paracrine manners.