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Biomedical subjects

G L Holmes

Publications and source records attributed to G L Holmes.

At least 19 recordsLinked to original sources
PubMed1992

Behavioral effects of continuous hippocampal stimulation in the developing rat.

There is controversy as to whether prolonged seizures are more detrimental to the immature than the mature brain. To evaluate this question continuous hippocampal stimulation was used to induce prolonged limbic seizures in 20-, 30- and 60-day-old rats. The long-term effects on learning and activity level were then studied at age 80 days using the Morris water maze, a test of spatial learning and memory, and the open field test, a test of an animal's reaction to a novel environment. Limbic status epilepticus in 60-day-old but not 20- and 30-day-old rats caused long-term impairment of learning in the Morris water maze. No differences were noted between the control and the experimental animals in the open field test. These results suggest that the age of seizure onset is an important determinant of long-term cognitive sequelae.

Animals↗
PubMed1992

Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures.

Acute and chronic effects of seizures induced by intraperitoneal (i.p.) injection of kainic acid (KA) were studied in developing rats (postnatal days (P) 5, 10, 20, 30, and adult 60). For 3 months following KA-induced status epilepticus, spontaneous recurrent seizure (SRS) occurrence was quantified using intermittent video monitoring. Latency to generalized seizures was then tested using flurothyl, and brains were histologically analyzed for CA3 lesions. In P5-10 rats, KA caused generalized tonic-clonic ('swimming') seizures. SRS did not develop, and there was no significant difference between control and KA-treated rats in latency to flurothyl-induced seizures. In contrast, rats P20 and older exhibited limbic automatisms followed by limbic motor seizures which secondarily generalized. Incidence and frequency of SRS increased with age. P20-30 rats with SRS had shorter latencies to flurothyl seizures than did KA-treated P20-30 rats without SRS or controls. KA-treated P60 rats (with or without SRS) had shorter latencies than controls to flurothyl seizure onset. SRS in P60 rats occurred sooner after KA than in P20-30 rats. CA3 lesions were seen in P20-60 rats with and without SRS, but not in P5-10 rats. These data suggest that there are developmental differences in both acute and chronic responses to KA, with immature animals relatively protected from the long-term deleterious effects of this convulsant.

Aging↗
PubMed1992

Effects of neural transplantation on seizures in the immature genetically epilepsy-prone rat.

To study the hypothesis that neural transplantations can alter seizure susceptibility in a genetic animal model of epilepsy, 93 pubescent genetically epilepsy-prone rats with stage 9 seizures received either bilateral inferior colliculi (N = 21) or lateral ventricle (N = 42) transplants or sham transplants (N = 30). The grafts consisted of embryonic locus ceruleus, neocortical, or cerebellar tissue. Starting 2 days after the transplantation the rats were subjected to audiogenic stimulations every other day for 61 days. Latency to the running and tonic phase, seizure severity score, and duration of the tonic and clonic phase were compared in the neural transplant and sham-operated controls. Rats that received transplants had a longer latency to the tonic phase and a shorter duration of the clonic phase than the controls. At age 110 days the rats had electrodes implanted bilaterally into the angular bundle and were kindled. No difference in kindling rate was found between the rats that received neural grafts and the sham-operated controls. Cerebrospinal fluid concentration of norepinephrine was not altered by the transplants. This study demonstrates that the anticonvulsant effects of neural transplants, using the genetically epilepsy-prone model of epilepsy, are mild.

Acoustic Stimulation↗
PubMed1992

Rolandic epilepsy: clinical and electroencephalographic features.

Benign rolandic epilepsy (BRE) is a common seizure disorder confined solely to children. The disorder is marked clinically by nocturnal generalized tonic-clonic seizures and diurnal seizures consisting of simple partial seizures consisting of brief unilateral facial clonic activity, dysphasia, and drooling. The EEG abnormalities are unique, consisting of generally high amplitude, centrotemporal spikes that are activated by sleep. The seizures typically begin in the first decade and almost always stop by age 16 years. The seizures are usually infrequent although clusters of seizures do occur. When the physician elects to treat, the seizures are usually easily controlled.

Adolescent↗
PubMed1991

Effect of neural transplants on seizure frequency and kindling in immature rats following kainic acid.

To study the hypothesis that neural transplantations can alter seizure susceptibility in a chronic animal model of epilepsy 260 immature rats (30- to 32-days-old) were administered a convulsant dosage of kainic acid (KA). Ten days later rats that had severe seizures following KA received either bilateral intracerebroventricular transplants of hippocampal (n = 27), neocortical (n = 29), cerebellar (n = 30), or locus ceruleus (n = 32) tissue, or underwent sham transplantation (n = 66). Spontaneous seizure frequency was assessed for 230 days following which the rats underwent entorhinal kindling. The percentage of rats developing spontaneous recurrent seizures was similar in the 4 transplant groups and the sham-operated controls. Rats receiving hippocampal and locus ceruleus transplants had fewer spontaneous seizures than the sham-operated controls or other transplant groups. However, there were no differences in afterdischarge thresholds or kindling rates in the 5 groups. This study demonstrates that the anticonvulsant effects of neural transplants, using this animal model are mild. Tissue type of the graft appears to be an important variable in the alteration of seizure frequency.

Animals↗
PubMed1991

The long-term effects of seizures on the developing brain: clinical and laboratory issues.

The long-term effects of seizures on the developing brain is a difficult clinical problem to study since cognitive impairment and behavioral abnormalities may be related to the etiological agent responsible for the seizures, age at time of onset of seizures, the type, frequency, or duration of the seizures, or the antiepileptic drugs used to treat the seizures. Many of these variables can be eliminated by using animal models of epilepsy. Work in our laboratory using the kainic acid (KA) model has demonstrated that status epilepticus in prepubescent and mature rats leads to significant deficits in memory, learning and behavior as adults when compared to control littermates without seizures. These rats also had a high incidence of spontaneous recurrent seizures (SRS) and an increased susceptibility to seizures using kindling and flurothyl. However, younger animals (less than or equal to 20 day old) with KA-induced seizures of similar severity were not associated with later neurological deficits. The immature animals also had a low rate of SRS and did not differ from controls in susceptibility to kindling or flurothyl. Studies using the continuous hippocampal stimulation model of epilepsy have also demonstrated that prolonged seizures in the developing brain are less severe than those in the mature animal. The pathophysiological mechanisms that "protect" the young brain from long-term detrimental effects of prolonged seizures are unknown.

Animals↗
PubMed1991

Effect of non-sex hormones on neuronal excitability, seizures, and the electroencephalogram.

Several of the non-sex hormones have been found to be useful in the treatment of seizures. These hormones have an effect on seizures, and seizures have an effect on these hormones. Adrenocorticotropic hormone (ACTH) and corticosteroid drugs have been found to be useful in the treatment of infantile spasms and other seizure disorders. Unfortunately, there is no clear consensus regarding superiority of ACTH versus prednisone in regard to efficacy and long-term benefits, dosage, or duration of treatment. There is also considerable debate regarding reasons why ACTH and prednisone are useful in infantile spasms, their mechanism of action, and their long-term effects on brain development. Thyrotropin-releasing hormone also has been used in the treatment of infantile spasms and other seizure types in children, with modest success. As with ACTH and prednisone, the mechanisms of action remain unclear.

Adrenal Cortex Hormones↗
PubMed1991

Do seizures cause brain damage?

Children with epilepsy are at significant risk for cognitive impairment and behavioral abnormalities. In most children with epilepsy, the likely reason for cognitive impairment is the underlying pathology responsible for the seizures. However, there is considerable controversy about whether seizures per se can cause brain damage or increase subsequent susceptibility to seizure. Although some longitudinal studies have related a decline in intellectual abilities to continued seizures, other studies indicate that treatment with antiepileptic drugs or progression of the encephalopathic process is responsible for the decline. Both clinical and animal studies have focused on the long-term effects of seizures on the developing brain. Whereas prolonged seizures may cause permanent neurologic sequelae in the mature animal, the immature brain may be more resistant to the long-term sequelae of seizures.

Abnormalities, Drug-Induced↗
PubMed1991

Comparison of factor-analyzed Adolescent Reinforcement Survey Schedule (ARSS) responses from Japanese and American adolescents.

The Adolescent Reinforcement Survey Schedule (ARSS) was administered to a sample of male and female late adolescent college students from Japan (N = 500). The responses to the ARSS are factor analyzed using a principal component method. The results of the factor-analyzed ARSS from the Japanese sample are compared and contrasted with the results from a previous study (Holmes et al., 1987) in which ARSS was administered to a sample of American male and female college students (N = 231). Both the American and Japanese samples produced 10 interpretable factors. A recommendation is made to replicate the present study with groups of early and mid-adolescents in each culture in order to study shifts in reinforcers during different periods of adolescent development.

Adolescent↗
PubMed1990

Epilepsy surgery in children.

Epilepsy surgery is becoming an increasingly used therapy for children with severe, medically intractable seizures. Temporal lobe ablation, corpus callosotomy, and hemispherectomy are currently the most commonly performed procedures. In this review the presurgical evaluation of patients with medically intractable seizures is described and risks and benefits of the surgery discussed. In selected patients temporal lobectomies and hemispherectomies may totally eliminate seizures while corpus callosotomies frequently reduce number and severity of generalized seizures.

Animals↗
PubMed1990

The effect of regional differences in noradrenergic neuron growth patterns on juvenile kindling.

Kindling can be altered by a variety of lesions designed to deplete norepinephrine (NE). However, the effect of the regional alteration in NE concentration on seizure susceptibility has not been studied. Two different concentrations of 6-hydroxydopamine (6-OHDA) were administered to one-day-old rat pups. At age 18 days, rat with significant rostral brain NE loss, due to high dose 6-OHDA, had a faster rate of electrical kindling in the entorhinal cortex than controls. In contrast rats receiving low dose 6-OHDA which resulted in comparable forebrain NE depletion but with a dramatic hindbrain noradrenergic overgrowth showed no enhancement of kindling. These results suggest that in the immature rat the proconvulsant effect of forebrain NE depletion can be overridden by an augmentation of hindbrain NE growth patterns.

Adrenergic Fibers↗
PubMed1990

Effects of seizures on learning, memory, and behavior in the genetically epilepsy-prone rat.

To determine whether frequent seizures can cause deficits in learning and behavior, immature genetically epilepsy-prone rats (GEPRs) were subjected to 66 audiogenic stimulations (Group 1). GEPR littermates were handled and placed in the sound chamber but were not stimulated (Group 2). Group 3 comprised genetically epilepsy-resistant rats (GERRs) who received audiogenic stimulations but had no seizures. After 3 weeks of stimulations the rats were tested for learning, memory, and behavior using the T-maze, water maze, open field activity test, home cage intruder test, and handling test. When compared with the control GEPRs and GERRs, Group 1 rats reached criteria less frequently in the T-maze, required longer times to find the platform in the water maze, and were less active in the open field activity test, less aggressive in the home cage intruder test, and more irritable and aggressive in the handling test. This study demonstrates that frequent, brief seizures in immature animals result in significant detrimental changes in learning, memory, activity level, and behavior.

Acoustic Stimulation↗
PubMed1990

Gaze-evoked involuntary movements.

Voluntary gaze may evoke a number of neurological phenomena such as vertigo, tinnitus, blepharoclonus, eyelid nystagmus, "facial nystagmus," involuntary laughter, and seizures. We report two patients in whom eccentric gaze evoked facial twitching and arm movement. Electroencephalograms remained unchanged during these movements. The pathogenesis of these movements is unclear but may involve ephaptic transmission.

Aged↗
PubMed1990

Effect of 2-amino-7-phosphonoheptanoic acid (APH) on seizure susceptibility in the prepubescent and mature rat.

There is now considerable evidence that the N-methyl-D-aspartic acid receptor is important in the genesis of seizures. One of the selective antagonist of the NMDA receptor is 2-amino-7-phosphonoheptanoic acid (APH). In this study we evaluated the effects of intracerebroventricular (i.c.v.) administration of APH on seizure susceptibility in both prepubescent and mature rats using the rapid kindling and flurothyl ether seizure models. Both the immature and mature animals receiving APH kindled at a significantly slower rate than control animals receiving phosphate-buffered saline. APH also demonstrated a significant anticonvulsant effect against flurothyl-induced seizures in both the immature and mature animals. This study supports prior work that selective NMDA receptor antagonists such as APH may have promise as potential antiepileptic agents.

2-Amino-5-phosphonovalerate↗
PubMed1990

Benign neonatal seizures.

Benign neonatal seizures is a rare but increasingly recognized syndrome characterized by seizures in the neonatal or infantile period. Two forms are recognized: familial and nonfamilial. In both instances, the seizures may be quite severe, and status epilepticus is common. The nonfamilial form is characterized by idiopathic, self-limited seizures occurring in previously normal neonates. The seizures most commonly occur at day 5 and have been called "fifth-day fits" by some authors. Familial seizures most frequently have their onset during the first week of life, but onset may occur as late as early infancy. These seizures may recur for several months before resolving. No cause is found for the seizures, and the patient appears healthy during the interictal period. The family history reveals benign neonatal seizures in other family members. Although the prognosis is favorable in both syndromes, seizures may occasionally occur later in life in the familial form. The familial form of benign neonatal seizures is autosomal dominant, and the gene has been localized to chromosome 20.

Electroencephalography↗