Biomedical subjects
G R Ullal
Publications and source records attributed to G R Ullal.
Relationship of rectal & hippocampal temperature profiles to seizure activity in rats prone & resistant to hot water induced epilepsy.
The present study evaluates the relationship of seizure proneness, to core body and brain temperature following hot water stimulation with water of 55 degrees C in freely ambulant rats. The rectal and hippocampal temperatures were recorded in 40 rats with bathing that included the head, while 10 other rats had similar thermal stimulation, but of the body alone. Bipolar stainless steel electrodes were stereotactically implanted into the dorsal hippocampal regions which served the dual purpose of recording the seizure discharges as well as regional brain temperature. It was observed that in the seizure prone (SP) rats, the mean rate of rise in rectal temperature was 1.5 degrees C/min, whereas in the seizure resistant (SR) animals it was 0.78 degree C/ min. However, there was no noticeable difference in the rate of rise in brain temperatures between the SP and SR groups, the rate of rise being 0.3 degree C/min. In the rats subjected to hot water bath over the body (excluding the head), there was no seizure activity. Further, there was no change in the brain temperature recorded in these rats, despite the rate of rise in rectal temperature being similar to that in the SP rats. These observations indicate that two thermoregulatory factors operate in seizure proneness-viz., a rapid rise in core body temperature; and a rise in local brain temperature. Both should coexist in order to elicit a hyperthermic seizure in rats.
Hyperthermic seizures: an animal model for hot-water epilepsy.
Freely ambulant wistar adult rats of both sexes when exposed to a hot water jet on the head (50 degrees C - 55 degrees C) for a period of 8-10 minutes, manifested seizure activity similar to the ones noted in 'hot-water epilepsy' (HWE) in humans. Depth electrode recording from the hippocampus revealed seizure discharges during the ictus lasting from 34 seconds to three minutes, followed by low voltage indeterminate activity and a quiescent resting phase. Seizure initiation was noted to be critically dependent on the rectal temperature of 41.5 degrees C and regional hippocampal temperature of 37 degrees C. There appeared to be no clear evidence for kindling phenomenon. Intervention of hyperthermia by cooling the body after the ictus prevented subsequent occurrence of spontaneous seizures. Pathological study of the brain revealed ischaemic changes in specific topographic areas like Sommer's sector in hippocampus, layer 4 and 5 neurons of the cerebral cortex and reticular neurons in the brain stem- a pathological feature reminiscent of the human epileptic brain. Seizure initiation by hyperthermic stimulation with hot water poured over the head, the progression and the EEG recording the seizure activity in these rats appears to resemble the HWE in human subjects and could thus serve as the first animal model for this form of "reflex' epilepsy. This has given new insight into the understanding of human HWE. Our preliminary observations in humans has suggested that HWE is a type of hyperthermic seizure similar to febrile convulsion but differs from it with respect to stimulus and rate of rise in temperature in a susceptible individual.
Effect of antiepileptic drugs and calcium channel blocker on hyperthermic seizures in rats: animal model for hot water epilepsy.
Hyperthermic seizures were elicited in groups of freely ambulant rats with jets of hot water of 55 degrees C on the head for about 10 mins. Bipolar depth EEG from the hippocampus and the behavioural seizures following the stimulation were recorded. The rectal temperature (threshold) for seizure initiation was 41.5 degrees C. The seizures were predominantly clonic jerks accompanied by large spikes and slow waves lasting for 30-60s. After 3 stimulations (once a day), Phenobarbitone (Pb) 0.02 mg/g daily, Diphenylhydantoin (DPH) 0.001 mg/g, 0.005 mg/g and 0.04 mg/g. daily and Nifedipine (Nif) 0.005 mg/g twice daily were administered intraperitoneally in different rats. During the 10-days injection trials, Pb completely suppressed seizures whereas DPH and Nif did not have any effect. One of the rats with DPH showed increased epileptic activity. After a 10 day 'washout' period' Pb and DPH were interchanged and again the rats were tested for seizures on 10 days. On changing over to Pb from DPH there was complete suppression of seizures and electrical seizure discharges. Whereas those rats which earlier had no seizure activity with Pb started showing the same on changing over to DPH.
Dihydropyridine group of calcium channel antagonist in epilepsy.
Effects of intraperitoneally administered dihydropyridine calcium channel blocker-nifedipine (NIF) 5 mg/kg and diphenylhydantoin (DPH) 5 mg/kg were studied on hippocampal kindling and maximum electro shock thresholds (MEST). All the NIF injected rats showed complete suppression of behavioral seizure after the 3rd injection. Few of the DPH rats had increased epileptic activity for two days and others--absence of Grade--5 seizure after the 5th DPH injection. However, all showed partial seizure suppression subsequently. Neither NIF nor DPH could suppress the after discharge (AD). MEST were not affected by NIF although DPH showed a complete suppression of posterior limb extensor tone in all the rats.
A neural network model for kindling of focal epilepsy: basic mechanism.
A simple neural network model is proposed for kindling--the phenomenon of generating epilepsy by means of repeated electrical stimulation. The model satisfies Dale's hypothesis, incorporates a Hebb-like learning rule and has low periodic activity in absence of shocks. Many of the experimental observations are reproduced and some new experiments are suggested. It is proposed that the main reason for kindling is the formation of a large number of excitatory synaptic connections due to learning.
Low frequency stimulation induces an increase in after-discharge thresholds in hippocampal and amygdaloid kindling.
In rats with electrodes implanted in the hippocampus or amygdala, the effect was studied of a single episode of low frequency stimulation (125 msec, biphasic 4 Hz, for 1 min at a current 50% of threshold for after-discharge), LFS, on the after-discharge thresholds (ADTs) during the course of hippocampal and amygdaloid kindling. ADTs were significantly increased following the LFS. The effect lasted longer (hippocampus, 12 days; amygdala, 5 days) when the LFS was given on day 1 of kindling than when kindling was fully established (less than 24 h).
Transferability of electro-convulsive shock induced short term memory impairment by brain homogenates in rats.
Six rats were subjected to a series of five electro-convulsive shocks. Their brain extracts were injected intraperitoneally into six other rats trained to perform a short term memory task. They showed a significant short term memory impairment after twentyfour hours and fortyeight hours and also, a difficulty in learning the task. The controls which consisted of rats injected with brain extracts of rats not subjected to any fits showed good memory trace and capacity to build up their memory. In this connection a new single-trial technique for short term memory was devised and standardised based on rat-trap principle and avoidance of unpleasant experience. Further, it was noticed that rats subjected to direct fits ate less and consumed less water. Those injected with brain homogenates of convulsed rats however, seemed not to deviate from the normal.