User:Delldot/ep

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Epileptogeneis is a process by which a normal brain develops epilepsy.[1] Epileptogenesis is a gradual process that occurs after an acute brain insult.[2] In epileptogenesis, an array of events occur on molecular and cellular levels that cause neurons to fire in a disordered manner and result in seizures.[3] Epileptogenesis can occur after brain insults such as traumatic brain injury (physical trauma to the brain), stroke, or status epilepticus (a prolonged seizure or series of seizures in quick succession).[2] Acquired vs. genetic

Canadian neurosurgeon Wilder Penfield called the time between injury and seizure "a silent period of strange ripening".[4] After a brain injury occurs, there is frequently a "silent" or "latent period" lasting months or years in which seizures do not occur; however, during this time, changes occur in the structure and physiology of the brain that result in the development of epilepsy.[2] It is this process in which hyperexciatble neural networks form that is referred to as epileptogenesis, and it is during this latent period that symptoms of epilepsy first occur.[2] If researchers come to better understand epileptogenesis, the latent period may provide a chance for healthcare providers to interfere with the development of epilepsy or reduce its severity.[2]

Contents

[edit] Hippocampus

Brain regions that are highly sensitive to insults that can cause epileptogenesis include the temporal lobe structures the hippocampus, the amygdala, and the piriform cortex.[2]

[edit] Cellular processes

Though the process is poorly understood, it is believed that activation of biochemical receptors on the surfaces of neurons is involved in epileptogenesis; these include the TrkB neurotrophin receptor and both ionotropic glutamate receptors and metabotropic glutamate receptors (those that are directly linked to an ion channel and those that are not, respectively).[1] Each of these types of receptor may, when activated, cause an increase in the concentration of calcium ions (Ca2+) within the area of the cell on which the receptors are located, and this Ca2+ can activate enzymes such as Src and Fyn that may lead to epileptogenesis.[1] In acquired epilepsy in both humans and animal models, increases in the amount of the neurotransmitter glutamate are observed, pyramidal neurons are lost, and new synapses are formed.[3]

Excessive release of glutamate is widely recognized as an important part of epileptogenesis early after a brain injury, including in humans.[2] Excessive release of glutamate results in excitotoxicity, in which neurons are excessively depolarized, intracellular Ca2+ concentrations increase sharply, and cellular damage or death results.[2] Excessive glutamatergic activity is also a feature of neuronal circuts after epilepsy has developed, but glutamate does not appear to play an important role in epileptogenesis during the latent period.[2]

Hyperexcitability, a characteristic feature of epileptogenesis in which the likelihood that neural networks will be activated is increased, may be due to loss of inhibitory neurons that would normally balance out the excitability of other neurons, such as GABAergic interneurons.[3] Neuronal circuits that are epileptic are known for being hyperexcitable and for lacking the normal balance of glutamatergic neurons (those that usually increase excitation) and GABAergic ones (those that decrease it).[2] In addition, the levels of GABA and the sensitivity of GABAA receptors to the neurotransmitter may decrease, resulting in less inhibition.[3] Other factors in hyperexcitability may include a decrease in the concentration of Ca2+ outside cells (i.e. in the extracellular space) and a decrease in the activity of ATPase in glial cells.[3]

Another proposed mechanism for epileptogenesis in TBI is that damage to white matter causes hyperexcitability by effectively undercutting the cerebral cortex.[5]

[edit] Role of blood

Blood that spills into brain tissue may play a role in the damage that results in epilepsy, perhaps by depositing hemosiderin or iron into the tissue.[5] Iron from hemoglobin that comes from blood can lead to the formation of free radicals that damage cell membranes, a process that has been linked to epileptogenesis.[6]

[edit] Research directions

Epileptogenesis that occurs in human brains has been modeled in a variety of animal models and cell culture models.[1] Epileptogenesis is poorly understood,[2] and increasing understanding of the process may aid researchers in preventing seizures, diagnosing epilepsy,[7] and developing treatments to prevent it.[1]

[edit] See also

[edit] References

  1. ^ a b c d e McNamara JO, Huang YZ, Leonard AS (October 2006). "Molecular signaling mechanisms underlying epileptogenesis". Sci. STKE 2006 (356): re12. doi:10.1126/stke.3562006re12. PMID 17033045. 
  2. ^ a b c d e f g h i j k Aroniadou-Anderjaska V, Fritsch B, Qashu F, Braga MF (February 2008). "Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy". Epilepsy Res. 78 (2-3): 102–16. doi:10.1016/j.eplepsyres.2007.11.011. PMID 18226499. 
  3. ^ a b c d e Armijo JA, Valdizán EM, De Las Cuevas I, Cuadrado A (2002). "Advances in the physiopathology of epileptogenesis: Molecular aspects" (in Spanish; Castilian). Rev Neurol 34 (5): 409–29. PMID 12040510. 
  4. ^ "Post-traumatic epilepsy" (1978). Br Med J 2 (6132): 229. PMID 98198. 
  5. ^ a b Firlik KS, Spencer DD (2004). "Surgery of post-traumatic epilepsy", in Dodson WE, Avanzini G, Shorvon SD, Fish DR, Perucca E: The Treatment of Epilepsy. Oxford: Blackwell Science, 775. ISBN 0-632-06046-8. Retrieved on 2008-06-09. 
  6. ^ Beghi E (2004). "Aetiology of epilepsy", in Dodson WE, Avanzini G, Shorvon SD, Fish DR, Perucca E: The Treatment of Epilepsy. Oxford: Blackwell Science, 61. ISBN 0-632-06046-8. Retrieved on 2008-06-09. 
  7. ^ Leśkiewicz M, Lasoń W (2007). "The neurochemical mechanisms of temporal lobe epilepsy: an update" (in Polish). Prz. Lek. 64 (11): 960–4. PMID 18409413. 


Category:Neurology Category:Neurotrauma