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Thomas P Sutula

Publications and source records attributed to Thomas P Sutula.

10 recordsLinked to original sources
PubMed2005

Models of epilepsy in the developing and adult brain: implications for neuroprotection.

Repeated seizures cause a sequence of molecular and cellular changes in both the developing and adult brain, which may lead to intractable epilepsy. This article reviews this sequence of neuronal alterations, with emphasis on the kindling model. At each step, the opportunity exists for strategic intervention to prevent or reduce the downstream consequences of epileptogenesis and seizure-induced adverse plasticity. The concept of seizure-induced brain damage must be expanded to include behavioral and cognitive deficits, as well as structural neuronal damage and increased predisposition to seizures.

Adult↗
PubMed2004

Seizures in the developing brain cause adverse long-term effects on spatial learning and anxiety.

PURPOSE: Seizures in the developing brain cause less macroscopic structural damage than do seizures in adulthood, but accumulating evidence shows that seizures early in life can be associated with persistent behavioral and cognitive impairments. We previously showed that long-term spatial memory in the eight-arm radial-arm maze was impaired in rats that experienced a single episode of kainic acid (KA)-induced status epilepticus during early development (postnatal days (P) 1-14). Here we extend those findings by using a set of behavioral paradigms that are sensitive to additional aspects of learning and behavior. METHODS: On P1, P7, P14, or P24, rats underwent status epilepticus induced by intraperitoneal injections of age-specific doses of KA. In adulthood (P90-P100), the behavioral performance of these rats was compared with that of control rats that did not receive KA. A modified version of the radial-arm maze was used to assess short-term spatial memory; the Morris water maze was used to evaluate long-term spatial memory and retrieval; and the elevated plus maze was used to determine anxiety. RESULTS: Compared with controls, rats with KA seizures at each tested age had impaired short-term spatial memory in the radial-arm maze (longer latency to criterion and more reference errors), deficient long-term spatial learning and retrieval in the water maze (longer escape latencies and memory for platform location), and a greater degree of anxiety in the elevated plus maze (greater time spent in open arms). CONCLUSIONS: These findings provide additional support for the concept that seizures early in life may be followed by life-long impairment of certain cognitive and behavioral functions. These results may have clinical implications, favoring early and aggressive control of seizures during development.

Animals↗
PubMed2003

Ultrastructural features of sprouted mossy fiber synapses in kindled and kainic acid-treated rats.

The mossy fiber pathway in the dentate gyrus undergoes sprouting and synaptic reorganization in response to seizures. The types of new synapses, their location and number, and the identity of their postsynaptic targets determine the functional properties of the reorganized circuitry. The goal of this study was to characterize the types and proportions of sprouted mossy fiber synapses in kindled and kainic acid-treated rats. In normal rats, synapses labeled by Timm histochemistry or dynorphin immunohistochemistry were rarely observed in the supragranular region of the inner molecular layer when examined by electron microscopy. In epileptic rats, sprouted mossy fiber synaptic terminals were frequently observed. The ultrastructural analysis of the types of sprouted synapses revealed that 1) in the supragranular region, labeled synaptic profiles were more frequently axospinous than axodendritic, and many axospinous synapses were perforated; 2) sprouted mossy fiber synaptic terminals formed exclusively asymmetric, putatively excitatory synapses with dendritic spines and shafts in the supragranular region and with the soma of granule cells in the granule cell layer; 3) in contrast to the large sprouted mossy fiber synapses in resected human epileptic hippocampus, the synapses formed by sprouted mossy fibers in rats were smaller; and 4) in several cases, the postsynaptic targets of sprouted synapses were identified as granule cells, but, in one case, a sprouted synaptic terminal formed a synapse with an inhibitory interneuron. The results demonstrate that axospinous asymmetric synapses are the most common type of synapse formed by sprouted mossy fiber terminals, supporting the viewpoint that most sprouted mossy fibers contribute to recurrent excitation in epilepsy.

Animals↗
PubMed2003

Do epileptic seizures damage the brain?

PURPOSE OF REVIEW: The possibility that recurrent seizures in patients with poorly controlled epilepsy may produce neuronal damage and contribute to progressive functional and cognitive declines observed in some patients with epilepsy has major clinical and therapeutic implications for urgency of treatment and effective intervention to achieve complete control. RECENT FINDINGS: Advances in magnetic resonance imaging techniques, technical and conceptual advances in experimental analysis of neuronal death at the cellular and molecular level, and long-term neuropsychological observations have provided substantial new data and insights into phenomena of seizure-induced plasticity in neural circuitry that address the question "Do epileptic seizures damage the brain?" SUMMARY: The emerging perspective is that seizure-induced damage should be regarded not only as neuronal loss but as adverse long-term behavioral and cognitive consequences. This perspective provides a strong rationale for development of neuroprotective treatments to forestall adverse long-term consequences of repeated seizures, and for the importance of prompt, effective intervention that achieves complete seizure control.

Age Factors↗
PubMed2002

Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy.

During the past decade, it has become apparent that neural circuits undergo activity-dependent reorganisation. In pathological disorders with recurring episodes of excessive neural activity, such as temporal-lobe epilepsy, brain circuits can undergo continual remodelling. For clinical practice, seizure-induced remodelling implies that after a diagnosis of epilepsy, recurring seizures can cause continuing neural reorganisation and potentially contribute to progressive severity of the epilepsy and to cognitive and behavioural consequences. The alterations induced by seizures include neuronal death and birth, axonal and dendritic sprouting, gliosis, molecular reorganisation of membrane and extracellular-matrix proteins, and intermediates involved in cellular homoeostasis. These changes are influenced by genetic background and seizure type, thus identification of genetic risk factors should be a priority. Therapeutic modification of seizure-induced molecular and cellular responses offers new opportunities for intervention beyond seizure suppression.

Animals↗
PubMedDate not supplied

Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development.

Clinical and epidemiological studies have repeatedly demonstrated that a subset of patients with epilepsy have progressive syndromes with increasing seizure frequency and cumulative adverse effects despite optimal anticonvulsant therapy. Recent longitudinal imaging studies and long-term neuropsychological studies have confirmed that a substantial subset of people with epilepsy undergo progressive brain atrophy accompanied by functional declines that worsen with duration of epilepsy. As further evidence of the progressive and adverse effects of inadequately controlled epilepsy, chronic experimental models of epilepsy and the phenomenon of kindling have provided abundant evidence that neural circuits undergo long-term progressive structural and functional alterations in response to seizures. This long-term seizure-induced plasticity in neural circuits appears to be "bidirectional", inducing progressive damage while also inducing resistance to additional damage, as a function of timing or inter-seizure interval. Seizure-induced plasticity has pronounced age-dependence, and influences long-term cognitive consequences of seizures during early life and acquired susceptibility to epilepsy in adulthood. While it is clear from clinical and epidemiological studies that human epilepsy is a heterogeneous disorder and that not all epileptic syndromes are progressive, emerging results from studies of activity-dependent and seizure-induced plasticity and perspectives from "complex systems" analysis are providing new insights into systematic neurobiological processes that are likely to influence the progressive features of epileptic syndromes and patterns of progression in individual patients. The emerging perspective is that phenomena of plasticity and genetic background exert powerful effects in development and adulthood through regulation of activity-dependent structural and functional remodeling of neural circuitry, and that these effects not only influence progression and consequences of seizures, but also offer new opportunities for therapeutic intervention.

Anticonvulsants↗