Biomedical subjects

J Cavazos

Publications and source records attributed to J Cavazos.

4 recordsLinked to original sources

PubMed1992

Assessing the functional significance of mossy fiber sprouting.

In recent years, a variety of histological techniques have provided evidence that the mossy fiber pathway in the dentate gyrus undergoes sprouting and reorganization of its synaptic connections in association with kindling, other experimental models of epilepsy, and human epilepsy. Although the neural circuitry of the dentate gyrus has been identified as a site of cellular and molecular alterations that influence the development of epilepsy by kindling, the functional effects of mossy fiber synaptic reorganization have not been defined. There has been rapid progress in the characterization of morphological alterations induced by seizures in the dentate gyrus and other pathways, but information on many fundamental aspects of hippocampal organization that could influence excitability are not available. Emerging evidence which suggests a possible link between synaptic reorganization and functional alterations in hippocampal circuitry needs to be considered in the context of limited information about critical details of hippocampal organization, the growing evidence for a diversity of seizure-induced cellular and molecular alterations that may alter excitability, and with awareness that mechanisms for generation of seizures may vary at different stages in the evolution of kindling and other epileptic syndromes. Efforts to characterize the role of synaptic reorganization and other specific cellular and molecular alterations in the generation of epileptic activity need to address this variety and complexity of potential mechanisms.

Afferent Pathways↗

PubMed1992

Alteration of long-lasting structural and functional effects of kainic acid in the hippocampus by brief treatment with phenobarbital.

Kainic acid, an analog of the excitatory amino acid L-glutamate, induces acute hyperexcitability and permanent structural alterations in the hippocampal formation of the adult rat. Administration of kainic acid is followed by acute seizures in hippocampal pathways, neuronal loss in CA3 and the hilus of the dentate gyrus, and reorganization of the synaptic connections of the mossy fiber pathway. Rats with these hippocampal structural alterations have increased susceptibility to kindling. To evaluate the role of the acute seizures and associated hippocampal structural alterations in the development of this long-lasting susceptibility, rats that received intraventricular kainic acid were cotreated with phenobarbital (60 mg/kg, s.c., once daily). Treatment with this dose for 5 d after administration of kainic acid suppressed acute seizure activity, protected against excitotoxic damage in the dentate gyrus, reduced mossy fiber sprouting, and completely abolished the increased susceptibility to kindling associated with kainic acid. Brief treatment with phenobarbital modified the pattern of damage and synaptic reorganization in the dentate gyrus in response to seizure-induced injury, and altered the long-lasting functional effects associated with hippocampal damage. As phenobarbital treatment did not protect against neuronal damage in CA3 or other regions of the hippocampus, the circuitry of the dentate gyrus was implicated as a locus of cellular alterations that influenced the development of kindling. These observations are evidence that pharmacological intervention can prevent the development of epilepsy in association with acquired structural lesions, and suggest that pharmacological modification of cellular responses to injury can favorably alter long-term functional effects of CNS damage.

Animals↗

PubMed1989

Mossy fiber synaptic reorganization in the epileptic human temporal lobe.

The distribution of the mossy fiber synaptic terminals was examined using the Timm histochemical method in surgically excised hippocampus and dentate gyrus from patients who underwent lobectomy of the anterior part of the temporal lobe for refractory partial complex epilepsy. The dentate gyrus of epileptic patients demonstrated intense Timm granules and abundant mossy fiber synaptic terminals in the supragranular region and the inner molecular layer. In contrast, the dentate gyrus of presenescent nonepileptic primates demonstrated no Timm granules in the supragranular region. In nonepileptic senescent primates, occasional very sparse supragranular Timm granules were results are morphological evidence of mossy fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganization induced by repeated partial complex seizures may play a role in human epilepsy.

Adolescent↗

PubMed1988

Synaptic reorganization in the hippocampus induced by abnormal functional activity.

Abnormal functional activity induces long-lasting physiological alterations in neural pathways that may play a role in the development of epilepsy. The cellular mechanisms of these alterations are not well understood. One hypothesis is that abnormal activity causes structural reorganization of neural pathways and promotes epileptogenesis. This report provides morphological evidence that synchronous perforant path activation and kindling of limbic pathways induce axonal growth and synaptic reorganization in the hippocampus, in the absence of overt morphological damage. The results show a previously unrecognized anatomic plasticity associated with synchronous activity and development of epileptic seizures in neural pathways.

Animals↗