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M E Blue

Publications and source records attributed to M E Blue.

41 records · Page 3Linked to original sources
PubMedDate not supplied

Effects of neonatal cholinergic basal forebrain lesions on excitatory amino acid receptors in neocortex.

The role of cholinergic basal forebrain projections in the modulation of cortical plasticity and associated functional changes is currently the subject of renewed attention. Excitatory amino acid receptors have been identified as mediators of cortical topographic efferent and afferent information. In addition some of these receptors, notably the NMDA and metabotropic [mGluR] type, participate in cortical plasticity. Growing evidence suggests that interactions between cholinergic and glutamatergic systems contribute to cognitive cortical functions and their anatomical and physiological substrates. Though cholinergic and glutamatergic mechanisms have both been shown to be involved in cortical morphogenesis, few studies have attempted to study their interactions in development. The present study investigates the effect of neonatal lesions to the cholinergic basal forebrain on NMDA, AMPA and mGluR receptors in BALB/CByJ mice, at two different developmental ages. We demonstrated previously that nBM lesions at birth result in transient cholinergic depletion for the first two postnatal weeks, substantial morphogenetic alterations in neocortex and cognitive deficits by adulthood. We show here that unilateral neonatal lesions result in decreases in NMDA and AMPA receptors but increases in mGluRs during the second postnatal week (PND 14). At 30 days postnatal, lesion mediated changes were attenuated, compared with PND 14, but significant sex differences in control and nBM lesioned mice were apparent. These data support the notion that cholinergic/glutamatergic interactions are important during early cortical morphogenesis. Moreover, our results highlight the fact that cholinergic as well glutamatergic developmental mechanisms are sexually dimorphic.

Acetylcholine↗
PubMedDate not supplied

A comparison of pattern formation by thalamocortical and serotonergic afferents in the rat barrel field cortex.

In the present study we compare the formation of vibrissa-related patterns by thalamocortical afferents from the ventrobasal (VB) nucleus to that by raphe-cortical, serotonergic afferents from the raphe nuclei. In opposite hemispheres of the same brain, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labeling of VB afferents and serotonin (5-HT) immunohistochemistry reveal that the pattern of vibrissa-specific patches is first exhibited by thalamocortical axons in barrel field cortex. Shortly thereafter, 5-HT axons form patches in the same locations as the dense concentrations of VB afferents. To assess a possible role of 5-HT afferents in the specification of barrel field cortex, neonatal rat pups were administered p-chloroamphetamine (PCA), a selective 5-HT neurotoxin. The formation of vibrissa-related patterns by thalamocortical and serotonergic afferents was compared in normal and PCA-treated rat pups at various developmental stages. PCA treatment led to a significant decrease in the number of serotonergic axons in barrel field cortex. Despite this decrease, VB afferents segregated in patches over individual barrels. However, a delay in the emergence of the thalamocortical pattern was noted in toxin-treated animals. We conclude that PCA treatment does not prevent formation of a vibrissa-specific pattern by thalamocortical afferents, and discuss the possibility that the 5-HT axons may play a trophic role in the maturation of VB afferents.

Animals↗
PubMedDate not supplied

Pathophysiology of cerebral injury and future management.

Central nervous system dysfunction continues to represent significant morbidity and associated mortality in patients undergoing cardiac surgery. Neurological dysfunction is most exaggerated in patients undergoing hypothermic circulatory arrest (HCA). Although surgical techniques, anesthetic management, and postoperative care have significantly improved over the past two decades, the incidence of stroke and other neurocognitive deficits remains problematic. Understanding the mechanisms of cell death associated with HCA may provide information that is germane to all types of cerebral injury involved in cardiac surgery. Using a closed-chest cardiopulmonary bypass model, dogs underwent 2 hours of circulatory arrest at 18 degrees C followed by resuscitation and recovery for 3 days. Animals were assessed functionally by a species-specific behavioral scale, histologically for patterns of selective neuronal necrosis and receptor autoradiography for NMDA glutamate receptor subtype expression. Using a selective NMDA (-glutamate) receptor antagonist (MK801), an AMPA-antagonist (NBQX) and a nonspecific neuroprotectant (GM1-ganglioside), the role of glutamate excitotoxicity in the development of HCA-induced brain injury was documented and validated. Using a similar canine preparation, a microdialysis technique was used to evaluate the role of nitric oxide in neuronal death. Arginine plus oxygen is converted to nitric oxide plus citrulline by the action of nitric oxide synthase. Simultaneous infusion of artificial cerebrospinal fluid containing L-[14C] arginine or L-[14C] arginine and L-NAME (a nitric oxide synthase inhibitor) was performed in contralateral hemispheres. Citrulline recovery in the cerebrospinal fluid, citrulline production in vitro from canine cortical homogenates, and nitric oxide metabolites in the serum were all significantly increased during HCA and reperfusion. These studies demonstrated that neurotoxicity following HCA involves a significant and early induction of neuronal NOS expression and neuronal processes leading to widespread augmented NO production in the brain. Continued research into the pathophysiologic mechanisms involved in cerebral injury will undoubtedly yield a safe and reliable neuroprotectant strategy.

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