Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli.
The amino acid glutamate, the major excitatory neurotransmitter in the central nervous system, activates receptors coupled to calcium influx. Excessive activation of glutamate receptors in conditions such as severe epileptic seizures or stroke can kill neurons in a process called excitotoxicity. However, subtoxic levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor elicit adaptive responses in neurons that enhance their ability to withstand more severe stress. A variety of stimuli induce adaptive responses to protect neurons. For example, sublethal ischemic episodes or a mild epileptic insult can protect neurons in a process referred to as tolerance. The molecular mechanisms that protect neurons by these different stressful stimuli are largely unknown but they share common features such as the transcription factor, nuclear factor kappa B (NF-kappaB), which is activated by ischemic and epileptic preconditioning as well as exposure to subtoxic NMDA concentrations. In this article, we describe stress-induced neuroprotective mechanisms highlighting the role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in neuronal survival and maintenance, neurogenesis and learning and memory.
Marini
A M
AM
Department of Neurology and Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. amarini@usuhs.mil
Jiang
X
X
Wu
X
X
Pan
H
H
Guo
Z
Z
Mattson
M P
MP
Blondeau
N
N
Novelli
A
A
Lipsky
R H
RH
D000222:Adaptation, Physiological; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007858:Learning; D008568:Memory; D016202:N-Methylaspartate / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D016328:NF-kappa B; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002118:Calcium