Abstract
Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Brain Injuries, Traumatic / pathology
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Brain Injuries, Traumatic / physiopathology
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Brain Injuries, Traumatic / prevention & control
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Craniocerebral Trauma / pathology
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Craniocerebral Trauma / physiopathology
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Craniocerebral Trauma / prevention & control*
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Diamines / pharmacology*
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Disease Models, Animal
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Down-Regulation / drug effects
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Male
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Neuroprotective Agents / pharmacology*
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Oxidative Stress / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Notch / antagonists & inhibitors*
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Receptors, Notch / genetics
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Receptors, Notch / metabolism
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Signal Transduction / drug effects
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Thiazoles / pharmacology*
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Transcription Factor HES-1 / antagonists & inhibitors
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Transcription Factor HES-1 / genetics
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Transcription Factor HES-1 / metabolism
Substances
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24-diamino-5-phenylthiazole
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Apoptosis Regulatory Proteins
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Basic Helix-Loop-Helix Transcription Factors
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Diamines
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Hes1 protein, rat
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Hes5 protein, rat
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Neuroprotective Agents
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RNA, Messenger
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Receptors, Notch
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Repressor Proteins
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Thiazoles
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Transcription Factor HES-1
Grants and funding
This study was financially supported by the "Emergency Diagnostic & Therapeutic Center of Central China.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.