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Biomedical subjects

M Dragunow

Publications and source records attributed to M Dragunow.

156 records · Page 9Linked to original sources
PubMed1987

8-Cyclopentyl 1,3-dimethylxanthine prolongs epileptic seizures in rats.

We tested the effects of 8-cyclopentyl-1,3 dimethylxanthine (8-CPT) on electrically induced seizures in rats. 8-CPT prolonged secondary seizures and converted partial seizures into generalized motor seizures, but did not affect primary seizure duration. Because 8-CPT is a potent and specific adenosine antagonist, these results add further support to the hypothesis that endogenous adenosine prevents the spread of epileptic seizures.

Animals↗
PubMed1987

Time-dependent effects of papaverine on electrically induced seizures in rats.

We tested the effects of papaverine, an adenosine uptake blocker, on hippocampal-elicited afterdischarges in rats. Rats were injected with 35 mg/kg papaverine and tested for seizure responses at 5, 20, and 60 min postinjection. Papaverine produced a potent inhibition of afterdischarge generation, greatly reduced afterdischarge duration, and blocked hippocampal-kindled seizures. This anticonvulsant effect was greatest 5 min postinjection and had largely dissipated by 60 min. Because papaverine also produced a Parkinson-like syndrome involving muscle rigidity, these results are discussed in terms of effects on dopamine and adenosine systems.

Adenosine↗
PubMed1987

Proconvulsant effects of theophylline on hippocampal afterdischarges.

We tested the effects of the adenosine antagonist, theophylline, on electrically induced afterdischarges in the hippocampus of rats. Theophylline did not significantly alter the threshold for afterdischarge initiation or the duration of the initial afterdischarge. However, theophylline greatly prolonged the duration of secondary afterdischarges, and permitted generalization to motor seizures. Because theophylline antagonizes adenosine, and the hippocampus is a region rich in adenosine binding sites, we interpret these results to mean that endogenous adenosine has little action on focal seizure initiation, but a strong action to suppress secondary seizures and to inhibit seizure generalization.

Animals↗
PubMed1986

Deep prepyriform cortex kindling and its relation to amygdala kindling in the rat.

Kindling of the deep prepyriform cortex (DPC), a recently identified sensitive site to chemoconvulsants, was compared to kindling of the amygdala in rats. Although the two kindled sites were very similar in their initial responses, electroencephalographic changes during kindling stimulation, kindling seizure development, and growth of afterdischarge, they differed in that the deep prepyriform cortex showed a significantly lower final threshold, a significantly higher frequency of afterdischarge and a significantly shorter latency to bilateral forelimb clonus than the amygdala. Significant bidirectional transfer was found during secondary kindling of either of the two sites, suggesting a close interrelation between them. Rhythmic synchronous discharge was directly induced in the deep prepyriform cortex by ipsilateral amygdala stimulation, but not in the amygdala by ipsilateral cortical stimulation. Local application of both muscimol (0.45 nM) and 2-amino-5-phosphonovaleric acid (25 nM) into the cortical site reduced the afterdischarge duration of amygdala-kindled seizures by approximately 20% without changing the type or duration of the motor seizure. We suggest that the deep prepyriform cortex is "downstream" from the amygdala in the preferential routes of afterdischarge propagation, and that, although the deep prepyriform cortical neurocircuits of GABA and excitatory amino acids may be involved in the maintenance of amygdala-kindled, self-sustained afterdischarge, they are not essential in the expression of amygdala-kindled motor convulsions.

2-Amino-5-phosphonovalerate↗
PubMed1986

Endogenous anticonvulsant substances.

Epileptic seizures will normally arrest abruptly and spontaneously, and the brain will remain refractory to further seizures for some time thereafter. This paper reviews the possible mechanisms underlying this seizure arrest and refractoriness. The data suggests that neuronal fatigue is not involved in either of these processes, whereas the role of ions and excitatory systems are unclear. Rather, seizure arrest and refractoriness may come about by the seizure-induced release and/or activity of multiple endogenous anticonvulsant substances. The spontaneous arrest of the seizure may involve the purine adenosine, in addition to other unknown mechanisms. Seizure refractoriness involves multiple systems, the most important of which, on the available evidence, are prostaglandins and opioid peptides and possibly benzodiazepine systems, although other neuropeptides and the purines may also be involved. The implications of these conclusions to anti-epileptic drug development and status epilepticus are discussed.

Animals↗
PubMed1984

Adenosine modulation of amygdala kindling.

To test the hypothesis that kindling is restrained by the inhibitory neuromodulator, adenosine, the adenosine uptake blocker, papaverine, or the adenosine antagonist, aminophylline, were injected systemically into rats 20 min before each daily electrical stimulation of the amygdala. The effects on amygdala-triggered seizures of papaverine, adenosine, 2-chloroadenosine, and the adenosine antagonists, isobutylmethylxanthine and caffeine, were also investigated at seizure threshold. Papaverine inhibited kindling, whereas aminophylline accelerated kindling. The adenosine agonists had anticonvulsant effects on seizures, and the antagonists had proconvulsant effects which involved, primarily, the lengthening of afterdischarge duration. Aminophylline injected repeatedly, in the absence of electrical stimulation, induced seizures. These results support the hypothesis that adenosine can modulate kindling and affect the seizure process.

2-Chloroadenosine↗
PubMed1983

Failure of dorsal bundle lesions in rats to increase distractibility to a low intensity tone.

Bilateral lesions of the dorsal noradrenergic bundle in rat brains with 6-hydroxydopamine produced a depletion of cortical noradrenaline to 19% of control values. Rats so treated showed resistance to extinction of a lever press task but no increased distractability from licking behaviour by a low intensity tone. These results cast doubt on the hypothesis that dorsal noradrenergic bundle lesions cause hyperdistractibility in rats.

Acoustic Stimulation↗
PubMedDate not supplied

Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus.

Alterations in neuronal gene expression have been proposed to account for permanent changes in brain function such as learning and memory. In particular, it has been suggested that protooncogenes such as c-fos may be rapidly induced in conditions that lead to neuronal plasticity and evoke permanent changes in the expression of effector genes. Concentrations of the c-fos proto-oncogene increase rapidly following depolarization-induced calcium influx in non-dividing neuronally differentiated PC 12 cells. Recently, the presence and induction of c-fos in the adult brain and spinal cord has been observed. Here we report that electrically-induced seizure activity, which leads to a permanent increase in the response of the brain to future seizures (kindling), rapidly and transiently increases c-fos protein-like immunoreactivity in the nuclei of granule cells in the rat dentate gyrus. These results suggest that c-fos protein is present within the nuclei of adult mammalian neurons, and could be involved in plastic changes in the nervous system associated with seizure activity.

Animals↗
PubMedDate not supplied

Is adenosine an endogenous anticonvulsant?

The anticonvulsant properties of adenosine were tested pharmacologically on amygdala-kindled seizure activity in rats. The adenosine analogue 2-chloroadenosine and the adenosine uptake blocker papaverine both increased the latency to behavioral clonus as well as reduced the duration and severity of the clonic motor convulsion. Both drugs, however, failed to alter the postkindling afterdischarge (AD) threshold. Theophylline, an adenosine antagonist, had the opposite effects, prolonging the AD and motor seizure durations and facilitating partially kindled seizures, but again not altering the prekindling or postkindling AD thresholds of amygdala-elicited seizures. In contrast, carbamazepine raised AD thresholds, suggesting that it does not produce its anticonvulsant effects through adenosine systems. Since endogenous adenosine can impede seizure spread and seizure continuation, but does not affect seizure initiation from the amygdala, perhaps endogenous adenosine has the special property of being brought into play as an anticonvulsant only by the seizure itself.

2-Chloroadenosine↗
PubMedDate not supplied

Apoptosis, neurotrophic factors and neurodegeneration.

Apoptosis is an active process of cell death characterized by distinct morphological features, and is often the end result of a genetic programme of events, i.e. programmed cell death (PCD). There is growing evidence supporting a role for apoptosis in some neurodegenerative diseases. This conclusion is based on DNA fragmentation studies and findings of increased levels of pro-apoptotic genes in human brain and in in vivo and in vitro model systems. Additionally, there is some evidence for a loss of neurotrophin support in neurodegenerative diseases. In Alzheimer's disease, in particular, there is strong evidence from human brain studies, transgenic models and in vitro models to suggest that the mode of nerve cell death is apoptotic. In this review we describe the evidence implicating apoptosis in neurodegenerative diseases with a particular emphasis on Alzheimer's disease.

Alzheimer Disease↗
PubMedDate not supplied

Unilateral vestibular deafferentation induces brain-derived neurotrophic factor (BDNF) protein expression in the guinea pig lateral but not medial vestibular nuclei.

The aim of the present study was to investigate the expression of the neurotrophin, brain-derived neurotrophic factor (BDNF), in the vestibular nucleus complex (VNC) following unilateral vestibular deafferentation (UVD). Using immunohistochemistry, BDNF expression was analyzed in the bilateral VNC of the guinea pig in sham animals, and immediately, 10 h, and 50 h post-UVD. No BDNF expression was seen in the VNC in sham animals or immediately or 10 h post-UVD. However, at 50 h post-UVD, clear BDNF expression was seen in the bilateral lateral vestibular nuclei (LVN) and in the bilateral abducens nuclei, but not in the medial vestibular nuclei (MVN). The significance of this late BDNF expression is nuclear.

Animals↗