Calpain-Dependent ErbB4 Cleavage Is Involved in Brain Ischemia-Induced Neuronal Death

No clue, so ask your doctor what this means in improving your recovery from your next stroke. If there seems to be no intention to followup, you need to call the hospital president and suggest that this doctor and probably the whole stroke department needs to be fired.  If we don't start demanding results and consequences for our poor stroke recoveries nothing will ever improve. Excuses will be offered, DO NOT ACCEPT THEM!  If this comment is offered, 'All strokes are different, all stroke recoveries are different', that alone is a fireable offense because it shows no understanding of cause and effect.
http://link.springer.com/article/10.1007/s12035-015-9275-2

• Ying-mei Lu,
• Yin-ping Gao,
• Rong-rong Tao,
• Mei-hua Liao,
• Ji-yun Huang,
• Gang Wu,
• Feng Han,
• Xiao-ming Li

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Abstract

Disturbance of neuregulin-1β/ErbB4 signaling is considered to be associated with brain ischemia, but the mechanisms of this disruption are largely unknown. In the present study, we provide evidence that degradation of ErbB4 is involved in neuronal cell death in response to ischemia. Our data showed that the application of neuregulin-1β provided significant protection against oxygen–glucose deprivation (OGD)-induced neuronal death as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V/propidium iodide flow cytometry analysis and terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) staining. Furthermore, neuregulin-1β treatment significantly reduced the infarct volume of ischemic mice, and this result was not seen in the ErbB4 knockout mice. We found that brain ischemia induced the breakdown of ErbB4 in a time-dependent manner in vivo, but not that of ErbB2. In vitro studies further indicated that recombinant calpain induced the cleavage of ErbB4 in a dose-dependent way, whereas the calpain inhibitor significantly reduced the OGD-induced ErbB4 breakdown. Additionally, OGD-induced apoptosis was partially abolished by transfection with the ErbB4_E872K mutant. Taken together, neuregulin-1β elicits its neuroprotective effect in an ErbB4-dependent manner, and the cleavage of ErbB4 by calpain contributes to a neuronal cell death cascade during brain ischemia.