Neuronal Excitability-Possible Cause of Migraine

Rate this post

A subtype of migraine with aura (Familial hemiplegic migraine) was studied and investigated using a mouse model having FHM2 to determine the cause of this migraine by the researchers of CNR institure of Neurosciece (Italy) and San Raffaele Scientific Institute (Milan).

Migraine Aura
Migraine attack accompanied by aura is found in 20-30% of migraine sufferers.Aura is a focal neurological phenomena which either precedes the attack or is accompanied by the attack. Duration of aura last for almost 60minutes, the headache phase of the attack begin within this 60 minures but in some cases it is delayed too.The symptoms of this migraine accompanied by aura can be motor or sensory.There is visual aura which occurs without headache, in this case there is disturbance of vision which includes vision consisting of zig zag lines, flashes of lights (black, white or multicolored), blurred vision and hemianopsia. Somatosensory aur, a pins and needles sensation experienced in areas of face, arm and hand. Hallucinations, illusion, tingling sensation are also other aura migraine symptoms usually seen.

Mechanism of FHM
FHM (Familial hemiplegic migraine) during aura includes weakness of the body along with some other complications like ataxi,seizures and coma.There are three genotypes of FHM among which this study was conducted using FHM2.FHM1(50% of FHM patients),FHM2( less than 25% of FHM patients) and FHM3(rare). Patients having FHM2 have mutations in the Na+/K+-ATPase gene ATP1A2.The researchers mutated this ATP1A2 gene by inserting W887R in mouse genome.

This mutated mouse was developed to study the affect of neuronal excitability. CSD (Cortical spreading  depression ) causes migraine aura and so this endophenotype was focused by the researchers in this study.CSD is a wave of cellular depolarization which slowly reaches to cerebral cortex causing aura.The trasmittence rate of this wave is 2-5mm/minute.Migraine aura is also the outcome of high potassium ion and glutamate concentration outside cell

CSD facilitaion in migraine
In the research conducted the mouse model created showed high CSD susceptibility.The increased CSD was due to the accelerated mutant protein degradation by the protease system of the cell,as a result the ?2 Na,K-ATPase protein amount also decreased.The ?2 Na,K pump has a specific role in the active glutamate reuptake from the synaptic cleft,this cleft is operated by glial cells and based on this the researches hypothesized that in the FHM2 mouse model CSD facilitation in the mouse model used was sustained by increased cortical excitory neurotransmission along with improper glutamate clearance.Based on this the authors proposed the vulnerability to CSD lies in the episodic problems in the excitation and inhibition balance.This disruptive balance is found in both normal migraine cases and in the rare FHM form too.