Period Of Status Epilepticus Research Articles

Neuroinfl ammatory Processes Affect Structural Changes in the Amygdala of Rats in a Lithium-Pilocarpine Model of Epilepsy

Temporal epilepsy is a severe neuromental disorder which is difficult to treat and whose pathogenesis is presumptively linked with the development of neuroinflammation, astrogliosis, and neuron death. The least studied of these processes occur in the amygdala, a part of the brain playing an important role in epileptogenesis. This study analyzes the structural and biochemical changes occurring in the basolateral part of the amygdala in a lithium-pilocarpine model of temporal epilepsy. Status epilepticus was induced in Wistar rats aged 7–8 weeks. Two subgroups were identified: one with severe, prolonged convulsions and one with mild short-lived convulsions. This separation was linked with the relationship between the probability of developing spontaneous recurrent convulsions in the chronic phase of the model on the one hand and the severity and duration of convulsions during the period of status epilepticus on the other. Histological studies were performed during the latent and chronic periods of the model (3 and 7 days and 2 months after administration of pilocarpine) using light and electron microscopy methods, as well as immunohistochemical analysis of the distribution of neuronal (Fox3) and glial (GFAP, Iba1) markers in cells. The expression of the genes for the proinflammatory cytokines interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa) was analyzed by reverse transcription and the real-time polymerase chain reaction on day 7 after status epilepticus. During the first week after administration of pilocarpine into the basolateral amygdala, rats with prolonged convulsions showed decreases in the number of neurons and significant increases in the numbers of astrocytes and microglial cells. Rats with short-term convulsions showed no glial reaction and cell death was less extensive. Ultrastructural studies demonstrated accumulations of lysosomes and other neurodegenerative changes in amygdalar neurons of rats with prolonged convulsions. These abnormalities were accompanied by increased expression of the Il1b and Tnfa genes, pointing to the development of neuroinflammatory processes. Changes found in amygdalar cells in rats with severe long-lasting convulsions could be among the key mechanisms of epileptogenesis and associated comorbid behavioral abnormalities.

CSF levels of a set of neurotrophic factors (brain-derived neurotrophic factor, nerve growth factor) and neuropeptides (neuropeptide Y, galanin) in epileptic children

This paper aims to investigate the possible roles of a set of neurotrophic factors (brain-derived neurotrophic factor-BDNF, nerve growth factor-NGF) and neuropeptides (neuropeptide Y-NPY, and galanin) in children with active epileptogenesis. The cerebrospinal fluid (CSF) levels of BDNF, NPY, NGF and galanin were measured with enzyme-linked immunosorbent assays in epileptic children (n = 73) and controls (n = 64). There were no significant alterations in the CSF levels of BDNF, NPY and NGF in epileptic children with active clinical seizures compared with the levels of controls. However profoundly depressed galanin levels were found in infants with epileptic encephalopathy (mean ± SD:0.63 ± 0.19 pg/ml) and significantly increased galanin levels were measured in children with drug resistant epilepsy during the period of status epilepticus (mean ± SD: 6.92 ± 1.19, pg/ml pg/ml) compared with the levels of controls. Depressed levels of galanin might reflect a defective anti-epileptogenic effect of galanin in infants with epileptic encephalopathy. On the contrary, increased CSF levels of galanin might be a result of anti-epileptogenic effects of this peptide in epileptic children with status epilepticus.

A new model for studying focal and generalized chronic seizures in anesthetized rats

Seizure activity in anesthetized animals can be recorded in a number of different animal models. One such model uses urethane as an anesthetic and kainic acid as a convulsant. In addition, it is known that animals can be made epileptic using kainic acid by causing a period of status epilepticus and waiting for epileptogenesis to occur. We report an animal model to study seizure activity in kainic acid‐induced epileptic rats under urethane anesthesia. Sprague‐Dawley rats were injected with sufficient kainic acid to cause a period of status epilepticus. At ≥8 months post status epilepticus, at a time when behavioral seizures were evident, the rats were anesthetized with urethane. EEG recordings from CA1 and CA3 were performed together with recordings of EKG, BP, and vagus nerve. All rats exhibited abnormal spiking in the EEG and 42% (5/12) experienced spontaneous focal seizures while under anesthesia. Spontaneous generalized seizure activity occurred in a subset of these animals. In 56% (5/9 tested), focal and generalized seizures could be triggered with brief trains of electrical stimuli. Vagus nerve activity was found to be increased during focal and generalized seizures. These results demonstrate a new animal model to study seizures, especially focal seizures of limbic cortical origin, in anesthetized epileptic rats with a variety of applications, including the study of autonomic activity during seizures.

MR Imaging and Quantification of the Movement of the Lamina Terminalis Depending on the CSF Dynamics

Brain pulsation is a well-known observation in neurosurgery, but methods for its visualization on MR imaging, like phase imaging, do not provide a detailed structural view. We prospectively investigated electrocardiographic (ECG)-gated cine true fast imaging with steady-state precession (FISP) sequence on volunteers to test a sequence for demonstrating brain pulsation and movements of intracranial structures related to CSF dynamics. Eleven healthy volunteers were investigated with prospectively ECG-gated cine true-FISP in the midsagittal plane. A total of 50 phases were recorded per cardiac cycle and per volunteer. The lamina terminalis was chosen to study the pulsatility of the brain, and the optic recess diameter was chosen for means of objective quantification of the degree of pulsatility. Pulsatile motion of the lamina terminalis was apparent in all volunteers on the cine mode. The mean diameter of the optic recess was 2.5 mm. The greatest change in diameter in 1 volunteer was 1.5 mm. The mean change in diameter was 40% during 1 cardiac cycle. Cine true-FISP sequence is a well-suited method for investigations of passive movements of the ventricular system. It shows pulsations of the brain as well as passive changes caused by CSF dynamics with high temporal and spatial resolution.

Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy

Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2–3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.

Subcellular distribution of Bcl-2 family proteins and 14-3-3 within the hippocampus during seizure-induced neuronal death in the rat

The molecular regulation of seizure-induced neuronal death may involve interactions between proteins of the Bcl-2 and 14-3-3 families. To further examine these pathways we performed subcellular fractionation on hippocampi obtained following a brief period of status epilepticus in the rat. Western blotting determined seizures induced caspase-8 cleavage and increased Bcl-w levels within the cytoplasm. Bax, Bad and Bid were largely present within the cytoplasm before and after seizures, although some Bax and, following seizures, truncated Bid was detected in mitochondria. Levels of 14-3-3 were significantly reduced in the cytoplasm and microsomal fractions. These data establish the expression and distribution profile of key Bcl-2 family proteins and the signaling chaperone 14-3-3 in the rat and provide additional evidence for the activation of programmed cell death pathways by seizures.

A Case Study of Alpers' Disease in Siblings

ABSTRACT.A 9-month-old boy presented with sudden onset of twitching of his left hand, foot, then face. The seizure subsequently became secondarily generalized. This was followed by a period of status epilepticus. His seizures were difficult to control, and included prolonged episodes of epilepsia partialis continua. This child's neurological condition progressed, with concomitant liver dysfunction, until death two months later. Serial EEGs were performed throughout the course of his illness.Twenty-two months later, this patient's 10½- month-old sister presented with a nearly identical onset of epilepsia partialis continua, also left-sided. Her liver function tests and biopsy showed findings similar to those of her brother, and the course of her illness was also similar. She died 4½ months after the onset of her symptoms.The clinical findings of these children fit well with those described by S. G. Boyd et al. (1986), and suggest that they suffered from “Alpers disease”. A review of this clinical entity, i...

Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage.

The influence of hyperthermia and hypothermia on epileptic brain damage was studied in rats, in which status epilepticus was induced by flurothyl. Histopathological changes were examined by light microscopy after 1 or 7 days of recovery. Two series of animals were studied. In the first, short periods of seizures (20 and 25 min) were employed to examine whether moderate hyperthermia (39.5 degrees C) would aggravate epileptic brain damage, and a longer period (45 min) was used to investigate whether moderate hypothermia (32.5 degrees C) would ameliorate the damage. The second series investigated whether brief periods of status epilepticus (10 min) would cause brain damage if hyperthermia were high or excessive. For this series, animals with body temperatures of 37.0, 39.0, and 41.0 degrees C were studied. Data from normothermic animals (37.5 degrees C) confirmed previously described neuronal damage. Although hyperthermic animals failed to show increased damage in the CA1 sector, or in the hilar region of the dentate gyrus, they showed enhanced damage in the neocortex and globus pallidus (GP). In substantia nigra pars reticulata (SNPR) four out of five hyperthermic animals had bilateral infarcts after 20 min of status epilepticus, whereas no normothermic animal showed such damage. Hypothermia seemed to ameliorate epileptic brain damage in the neocortex (n.s.) and GP (P < 0.05) following status epilepticus for 45 min. Three out of seven hypothermic animals had mild SNPR involvement compared to severe infarction of the nucleus in five out of six normothermic animals (P < 0.05). Thus, hyperthermia aggravated and hypothermia ameliorated epileptic brain damage both in regions showing selective neuronal necrosis (neocortex) and in regions developing pan-necrosis (GP and SNPR). The second series displayed an unexpected result of excessive hyperthermia. Animals subjected to only 10 min of status epilepticus at a temperature of 41 degrees C showed not only neocortical lesions, but also moderate to extensive damage to the hippocampus (CA1, subiculum, and dentate gyrus). It is concluded that at high body and brain temperature, brief periods of status epilepticus can yield extensive brain damage, primarily affecting the hippocampus.

Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage.

After long periods of status epilepticus, selective neuronal necrosis is incurred in the neocortex (layer III-IV), in the hippocampus (CA1 and CA4), and in the thalamus (VPL-VPM). In these areas the cerebral metabolic rate for glucose is increased to between 200-300% of control, indicating a correlation between neuronal damage and enhanced neuronal activity. Measurements of local cerebral blood flow indicate that the damage is not due to insufficient supply of oxygen. In most rats with status epilepticus lasting longer than 30 minutes, an infarction develops in the substantia nigra pars reticulata. In this region the metabolic rate is first increased but later during the seizure activity falls to very low values indicating cell necrosis. prolonged neuronal hyperactivity with a concomitant increase in the metabolic rate for glucose is a prerequisite for the development of neuronal damage. However, the necrosis of the SNPR demonstrates that other factors determine the vulnerability of neurons to hyperexcitation, e.g., the type of agonist acting on the neuron.

Status epilepticus, hypothermia and metabolic chaos in a man with agenesis of the corpus callosum.

A case of hypothermia and metabolic derangement in a 60-year-old man following a period of status epilepticus is reported. A CT head scan performed subsequently demonstrated agenesis of the corpus callosum. Hypercalcaemia which has not been reported before was a prominent abnormality in the metabolic profile.