Atipamezole, an alpha(2)-adrenoceptor antagonist, has disease modifying effects on epileptogenesis in rats.

Stimulation of alpha(2)-adrenoceptors delays the development of kindling, a model of epileptogenesis in humans. Blocking alpha(2)-adrenoceptors is proconvulsant, but has beneficial effects on somatomotor recovery after experimental stroke. We investigated whether atipamezole, a selective alpha(2)-adrenoceptor antagonist, affects the recovery process from status epilepticus (SE)-induced brain damage, which affects the risk of epileptogenesis.

Chromatin condensation during glutamate-induced excitotoxicity of cerebellar [correction of celebellar] granule neurons precedes disintegration of nuclear DNA into high molecular weight DNA fragments.

The disturbance of the intracellular ionic homeostasis after activation of channel-associated membrane receptors by the excitatory neurotransmitters represents a principle event that triggers excitotoxic cell death of neurons. Here we demonstrate that glutamate-induced excitotoxicity of cerebellar granule neurons was accompanied by apoptosis-like nuclear shrinkage, chromatin condensation, and disintegration of nuclear DNA into high molecular weight DNA fragments, but was neither associated with activation of caspase 1, -2, -3, -9, nor was protected by a pan-caspase inhibitor, zVAD-fmk. We further demonstrate that chromatin condensation took place at the early stages of excitotoxicity and preceded nuclear DNA fragmentation.

The role of topoisomerase II in the excision of DNA loop domains during apoptosis.

Disintegration of nuclear DNA into high molecular weight (HMW) and oligonucleosomal DNA fragments represents two major periodicities of DNA fragmentation during apoptosis. These are thought to originate from the excision of DNA loop domains and from the cleavage of nuclear DNA at the internucleosomal positions, respectively. In this report, we demonstrate that different apoptotic insults induced apoptosis in NB-2a neuroblastoma cells that was invariably accompanied by the formation of HMW DNA fragments of about 50-100 kb but proceeded either with or without oligonucleosomal DNA cleavage, depending on the type of apoptotic inducer.