Article activity feed

  1. Evaluation Summary:

    The authors demonstrate that patients carrying a gain-of-function S218L mutation in CACNA1A exhibit a gene-dosage-dependent increase in the susceptibility to cortical spreading depression (CSD), seizure activity and brain edema formation following TBI compared with wild-type (WT) mice or mice carrying the milder R192Q mutation. This paper will be of considerable interest to familial hemiplegic migraine (FHM) sufferers who experience traumatic brain injury (and their physicians), as well researchers with an interest in the spectrum and phenotypic consequences of mutations in the voltage-gated, P/Q-type Ca2+ channel, CACNA1A.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Was this evaluation helpful?
  2. Joint Public Review:

    The study "Mutated neuronal voltage-gated CaV2.1 channels causing familial hemiplegic 4 migraine 1 increase the susceptibility for cortical spreading depolarization 5 and seizures and worsen outcome after experimental traumatic brain injury" describes a higher susceptibility and number of cortical spreading depressions in mice bearing the S218L and R192Q mutations following experimental TBI induced by CCI. Increased number of CSD´S is associated with a slight increase in lesion size and edema. Moreover, a higher mortality was experienced in S218L transgenic mice. The study has been well conducted, the experimental procedures are well described.

    The study provides the first essential step in understanding the higher susceptibility of mice with respective mutations to acute brain injury. Further subsequent investigations will be required to unravel underlying cellular and subcellular mechanisms.

    Was this evaluation helpful?