Affiliations: Parkinson's and Movement Disorders Institute, Long
Beach Memorial Medical Center, Long Beach, CA 90801-1428, USA | Department of Neurology, and Community &
Environmental Medicine, University of California Irvine, Irvine, CA, USA
Note: [] Corresponding author: A.G. Kanthasamy, Research Administration Building, Parkinson's and Movement Disorders Institute, Long
Beach Memorial Medical Center, Long Beach, CA 90801-1428, USA. Tel.: +1 562 427 1834; Fax: +1 562 490 3738; E-mail: [email protected]
Abstract: A major consequence of severe cardiac arrest is impairment of
neurological functions. Posthypoxic myoclonus and seizures are two of the major
neurological problems following ischemic and hypoxic insults. This condition
affects motor function to different degrees of severity ranging from mild to
serious debilitation. The pathophysiological mechanism(s) associated with these
neurological conditions remain elusive. Glutamate-mediated neuronal
overexcitation is thought to play a major role in the neuronal damage and in
the neurological consequences of the posthypoxic state. Therefore, lamotrigine,
a new anticonvulsant that indirectly modulates glutamatergic neurotransmission
by interfering with voltage-dependent sodium channels, was tested for its
effectiveness in controlling the neurological and histopathological changes in
the animal model of cardiac arrest-induced myoclonus. Lamotrigine
dose-dependently attenuated the audiogenic seizures and action myoclonus seen
in this rat model. Histological analysis using Nissl staining and the novel
Fluoro-Jade histochemistry in cardiac-arrested rats showed an extensive
neuronal degeneration in the hippocampus and cerebellum. Lamotrigine treatment
significantly attenuated the neuronal degeneration in these brain areas. The
neuroprotective effect was more pronounced in hippocampal pyramidal and
cerebellar Purkinje neurons. The therapeutic window of lamotrigine in this
model was 8 hours. These results suggest that lamotrigine can be viewed as a
potential antimyoclonic and neuroprotective agent for the treatment of
posthypoxic myoclonus and seizures. The study also suggests that neuronal
hyperexcitability may play a role in the etiology of posthypoxic myoclonus and
seizure.
Keywords: myoclonus, Na+ channel, global ischemia, motor function, seizure, neuroprotection
