Experimental neurology
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Experimental neurology · Mar 2007
In vivo visualization of focal demyelination in peripheral nerves by gadofluorine M-enhanced magnetic resonance imaging.
Magnetic resonance imaging (MRI) allows assessment of axonal nerve lesions, but detection of focal demyelination is still difficult. We have recently shown that the novel micellar magnetic resonance (MR) contrast agent gadofluorine M (Gf) accumulates in nerve fibers undergoing Wallerian degeneration. In the present study, we report on the in vivo visualization of focal demyelination induced by lysolecithin. ⋯ Gf enhancement persisted until remyelination had occurred. Our study shows that areas of focal nerve demyelination can be detected in vivo by Gf-enhanced MRI. This finding opens up a broad spectrum of applications in experimental neurology, and, depending on further clinical development of Gf, may aid in the diagnostic work up of patients with patchy, multifocal demyelinative disorders in the future.
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Experimental neurology · Mar 2007
Impaired expression of postsynaptic density proteins in the hippocampal CA1 region of rats following perinatal hypoxia.
Perinatal hypoxia is an important cause of brain injury amongst the newborn, such injury often resulting in an increased risk of impaired performance as regards learning and memory in later life for the affected individual. The postsynaptic density 95 (PSD-95) protein is a cytoskeletal specialization involved in the anchoring of N-methyl-d-aspartate (NMDA) receptors in postsynaptic neurons and has been reported to serve several important functions (e.g., synaptogenesis, synaptic plasticity and learning and memory performance) for the mammalian brain. Herein we investigated the long-term effects of perinatal hypoxia upon the complex of PSD-95 with NMDAR subunits by means of downstream signalling cAMP response element binding protein (CREB) phosphorylation at the Serine-133 locus (CREB(Ser-133) phosphorylation) within the hippocampal CA1 area (an essential integration area for mammalian learning and memory) within test-rat brains, as well as the effects upon afflicted-individual long-term learning and memory performance. ⋯ In addition, activation of the D1/D5R via A68930 (a selective, CNS-permeable agonist of D1/D5Rs) administration (2 mg/kg/day, P17-23 inclusively) markedly attenuated the hypoxia-induced deleterious effects, suggesting an effective therapeutic efficacy for A68930. Our results demonstrate the long-term effects of perinatal hypoxia upon the developing brain and provide additional insights into the relative vulnerability of postsynaptic density (PSD) proteins to such insult, as well as the impairment of downstream transcription signalling CREB(Ser-133) phosphorylation following perinatal hypoxia. More importantly, D1/D5R activation following perinatal hypoxia may be an alternative therapeutic strategy to that which is currently available and may offer significant clinical potential for hypoxia sufferers.
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Experimental neurology · Mar 2007
Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration.
Cerebral inflammation and apoptotic cell death are two processes implicated in the progressive tissue damage that occurs following traumatic brain injury (TBI), and strategies to inhibit one or both of these pathways are being investigated as potential therapies for TBI patients. The tetracycline derivative minocycline was therapeutically effective in various models of central nervous system injury and disease, via mechanisms involving suppression of inflammation and apoptosis. We therefore investigated the effect of minocycline in TBI using a closed head injury model. ⋯ The early beneficial effect is likely not due to anti-apoptotic mechanisms, as the density of apoptotic cells is not affected at either time-point. However, protection by minocycline is associated with a selective anti-inflammatory response, in that microglial activation and interleukin-1beta expression are reduced, while neutrophil infiltration and expression of multiple cytokines are not affected. These findings demonstrate that further studies on minocycline in TBI are necessary in order to consider it as a novel therapy for brain-injured patients.
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Experimental neurology · Mar 2007
GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate pain-induced escape/avoidance behavior.
The rostral anterior cingulate cortex (rACC) is involved in supraspinal nociceptive processing. ACC lesions relieve persistent pain, but do not affect the patient's ability to localize a noxious stimulus. Since the rACC has a high density of GABA receptors, it is possible that pain processing is influenced by these receptors in the rACC. ⋯ The attenuation was specific to the rACC and was blocked by a preadministered microinjection of the appropriate antagonist(s) into the rACC. In conclusion, microinjection of GABA and higher doses of muscimol did not decrease mechanical hyperalgesia but did attenuate place escape/avoidance behavior that is associated with mechanical stimulation of the ligated paw. These results provide additional support for the role of the rACC in higher order supraspinal processing of noxious events and suggest that rACC GABA(A) receptors significantly contribute to this processing.
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Experimental neurology · Mar 2007
Heavy neurofilament accumulation and alpha-spectrin degradation accompany cerebellar white matter functional deficits following forebrain fluid percussion injury.
Evidence for diffuse traumatic axonal injury (TAI) in clinical cases and animal models of traumatic brain injury (TBI) indicate that pathophysiological mechanisms extend to regions remote from the injury epicenter. The potential for indirect cerebellar trauma contributing to TBI pathophysiology is of significance since impairment of motor function and coordination is a common consequence of TBI but is also a domain associated with cerebellar function. The relationship between cerebellar white matter structure and function following traumatic head injury has not been examined. ⋯ Evidence of heavy chain neurofilament (NF200) degradation was observed at 1 day post-injury by Western blot. Immunohistochemistry labeling for NF200 indicated the presence of highly immunoreactive NF200 axonal swellings consistent with morphological features of TAI. alpha-Spectrin degradation was also observed between 1 and 14 days post-injury. This study demonstrates the electrophysiological consequences of cerebellar white matter injury and a temporal profile of NF200 and spectrin degradation following forebrain FPI.