Focal and generalized seizures can influence autonomic nervous system (ANS) function. Flushing, sweating and piloerection are reported in some patients with simple partial seizures. A broader spectrum of autonomic signs, including changes in heart rate and rhythm (most often bradycardia), blood pressure (most often pressure increases), pupillary size, vasomotor and sudomotor activity, GI motility and secretion, is reported in patients with complex partial seizures. Generalized tonic-clonic seizures can be associated with severe increases in blood pressure and changes in heart rate (e.g. complete nodal block). In spite of an apparent pattern of increasing autonomic dysfunction with increasing seizure intensity, sudden death during a seizure is not limited to cases of status epilepticus or even generalized tonic-clonic seizures. It is possible that some seizures, particularly those that result in sudden death, cause dangerous autonomic over-activity. The extent of seizure-induced alterations in autonomic nervous system function, acutely and chronically, has not been well studied. It is not clear whether autonomic changes are entirely secondary to motor manifestations or if autonomic consequences are independent have motor activity, perhaps even being significant in a non-convulsive seizure. The short term goals of this pilot study are to determine experimentally the feasibilty of measuring peripheral parameters related to ANS function before, during and after seizures of different onset (focal vs. generalized) and duration; and to correlate changes with the types of seizures. We have developed a custom chronic recording system for long-term monitoring of blood pressure (BP), electrocardiogram (ECG), and peripheral nerve activity (sympathetic postganglionic axons) in freely-behaving rats to assess changes mediated by the autonomic nervous system. We will determine the feasibility of adapting our system to monitor autonomic parameters during 5 seizure conditions: a) focal seizures; b) focal seizures with secondary generalization; c) primarily generalized seizures; d) status epilepticus; and e) spontaneous seizures in a chronic seizure model. Specifically, we will compare focal with generalized seizures, and primarily generalized with secondarily generalized seizures. In animals that develop spontaneous seizures, we will compare triggered with spontaneous seizures. We will also correlate the duration of electroencephalographic seizure activity with the intensity of motor convulsions. Focal and secondarily generalized seizures will be studied in perirhinal kindled rats. Primarily generalized seizures will be studied in rats exposed to flurothyl gas. Status epileptics and spontaneous seizures will be studied in rats injected with kainic acid. Lastly, we will define whether any changes in autonomic parameters can predict the occurrence of sudden death in the fraction of animals that die during flurothyl-induced seizures. Defining seizure-induced autonomic changes will permit development of specific therapies to reduce or prevent some of the serious acute consequences of seizures, such as sudden death, and will improve understanding of the long-term consequences of repeated seizures.
| Orman, R; Stewart, M (2007) Hemispheric differences in protein kinase C betaII levels in the rat amygdala: baseline asymmetry and lateralized changes associated with cue and context in a classical fear conditioning paradigm. Neuroscience 144:797-807 |
| Bluestone, A Y; Stewart, M; Lei, B et al. (2004) Three-dimensional optical tomographic brain imaging in small animals, part 2: unilateral carotid occlusion. J Biomed Opt 9:1063-73 |
