Experimental neurology
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Respiratory failure is the leading cause of death after cervical spinal injury. We hypothesized that incomplete cervical spinal injuries would alter respiratory pattern and initiate plasticity in the neural control of breathing. Further, we hypothesized that the severity of cervical spinal contusion would correlate with changes in breathing pattern. ⋯ Thus, the severity of C4-C5 spinal contusion dictates post-injury breathing pattern. In anesthetized rats, phrenic burst amplitude was decreased on the side of injury, and burst frequency correlated negatively with contusion size (R(2)=0.51; p<0.05). A strong correlation between unanesthetized breathing pattern and the pattern of phrenic bursts in anesthetized, vagotomized and ventilated rats suggests that changes in respiratory motor output after spinal injury reflect, at least in part, intrinsic neural mechanisms of CNS plasticity initiated by injury.
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Experimental neurology · Sep 2011
Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter.
Inhibition of phospholipase A(2) (PLA(2)) has recently been found to attenuate the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis (MS). However, the protective mechanisms that underlie PLA(2) inhibition are still not well understood. In this study, we found that cytosolic PLA(2) (cPLA(2)) was highly expressed in infiltrating lymphocytes and macrophages/microglia in mouse spinal cord white matter. ⋯ AACOCF3 significantly attenuated iNOS induction, nitric oxide production and the generation of reactive oxygen species in reactive microglia. Similar to the decomposition catalyst of peroxynitrite, AACOCF3 also blocked oligodendrocyte toxicity induced by reactive microglia. These results suggest that AACOCF3 may prevent oligodendrocyte loss in EAE by attenuating peroxynitrite formation in the spinal cord white matter.
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Experimental neurology · Aug 2011
Blood-brain barrier disruption following subarchnoid hemorrhage may be faciliated through PUMA induction of endothelial cell apoptosis from the endoplasmic reticulum.
The blood-brain barrier (BBB) plays a vital role as both a physiologic and physical barrier in regulating the movement of water from the vasculature to the brain. During a subarachnoid hemorrhage (SAH), the BBB is disrupted by a variety of mediators, one of which can result in endothelial cell death. As a result, in the present study, we investigated the role of PUMA (p53 upregulated modulator of apoptosis) following SAH injury in rats. ⋯ This study showed that PUMA induced endothelial cell apoptosis may in fact play a significant role in BBB disruption following SAH and its mediation may be through the endoplasmic reticulum. By blocking the activity of PUMA using siRNA, we were able to prevent the accumulation of cerebral edema that occurs following BBB disruption. This translated into a preservation of functional integrity and an improvement in mortality.
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Experimental neurology · Aug 2011
Some lumbar sympathetic neurons develop a glutamatergic phenotype after peripheral axotomy with a note on VGLUT₂-positive perineuronal baskets.
Glutamate is the main excitatory neurotransmitter in the nervous system, including in primary afferent neurons. However, to date a glutamatergic phenotype of autonomic neurons has not been described. Therefore, we explored the expression of vesicular glutamate transporter (VGLUT) types 1, 2 and 3 in lumbar sympathetic chain (LSC) and major pelvic ganglion (MPG) of naïve BALB/C mice, as well as after pelvic nerve axotomy (PNA), using immunohistochemistry and in situ hybridization. ⋯ This was confirmed by the lack of expression of VGLUT(1) or VGLUT(3) mRNAs in LSCs, even after PNA or SNA. Taken together, axotomy of visceral and non-visceral nerves results in a glutamatergic phenotype of some LSC neurons. In addition, we show previously non-described MPG perineuronal glutamatergic baskets.
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Experimental neurology · Aug 2011
Nav1.7 accumulates and co-localizes with phosphorylated ERK1/2 within transected axons in early experimental neuromas.
Peripheral nerve injury can result in formation of a neuroma, which is often associated with heightened sensitivity to normally innocuous stimuli as well as spontaneous dysesthesia and pain. The onset and persistence of neuropathic pain have been linked to spontaneous ectopic electrogenesis in axons within neuromas, suggesting an involvement of voltage-gated sodium channels. Sodium channel isoforms Na(V)1.3, Na(V)1.7 and Na(V)1.8 have been shown to accumulate in chronic painful human neuromas, while, to date, only Na(V)1.3 has been reported to accumulate within experimental neuromas. ⋯ We demonstrate increased levels of Na(V)1.7 in experimental rat sciatic nerve neuromas, 2weeks after nerve ligation and transaction. We further show elevated levels of phosphorylated ERK1/2 within individual neuroma axons that exhibit Na(V)1.7 accumulation. These results extend previous descriptions of sodium channel and MAP kinase accumulation within experimental and human neuromas, and suggest that targeted blockade of Na(V)1.7 or ERK1/2 may provide a strategy for amelioration of chronic pain that often follows nerve injury and formation of neuromas.