Abstract

Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction. Studies also associated r-mTBI with “second-impact syndrome” and chronic traumatic encephalopathy (CTE) as possible consequences of r-mTBI. However, the potential injury mechanisms involved in r-mTBI still remain unclear and research on r- mTBI is still in early stages. Thereby, in this study an in vitro uniaxial stretching model was used to investigate the r-mTBI related cell damage for clarifying the pathology and post-injury sequelae of r- m TBI in comparison with single mTBI. 3 types of stretching experiments were conducted including the single loading groups that were subjected once to stretching with a strain of 0.1 at a strain rate of 5 s-1, the repetitive loading groups that were subjected again to the same stretching 1 h after the initial stretching, and the sham control groups that were set in and removed from the uniaxial stretching device without receiving mechanical loading. Results shows that even though initial insult induced some level of swelling formation, swelling formation increased by second stretching confirming that r-mTBI causes increased amounts of cellular damage when compared with single insults of the same magnitude. Moreover, the absence of progression to cell death at 24 h post injury is detected after swelling formation by repetitive stretching. These data indicate that if injured neurons are subsequently subjected to low strain at the same level, the rate of injury significantly increases confirming the emerging hypothesis on repetitive mTBI exacerbating traumatic axonal injury.

Keywords

repetitive mild traumatic brain injury, concussion, impulsive strain, axonal stretching, axonal swellings, cell death

Background

To this day, traumatic brain injury (TBI) continues to be a leading cause of mortality and morbidity worldwide, making TBI a significant public health problem [1]. In the United States alone, the estimated number for annual occurrence of TBI is 1,700,000 [2-3] whereas in Asia 300-400, and in European countries (average of the 23 countries) 200-300 people per 100 000 are hospitalized annually due to TBI [4-6]. Moreover, majority of these cases categorized as mild TBI (mTBI) or concussion [2, 7] while, in spite of the name “mild”, approximately 15% of mTBI patients suffering persistent cognitive dysfunction in the United States alone [8]. Furthermore, several studies on professional athletes and military personnel have reported that these cognitive dysfunctions become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after “repetitive” mTBI (r-mTBI), contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction [9-17]. Aiding to the human cases, studies on animal models have also demonstrated a worsened outcome with repetitive TBI, where cell death and tissue damage are common consequences of moderate and severe TBI, not mTBI, yet cellular dysfunction and memory deficits are overt after mTBI [18-22].

Methods

Abstract Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction.

Results

Abstract Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction.

Discussion

Abstract Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction.

Competing interests

Abstract Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction.

Authors' contributions

Abstract Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction.

Acknowledgements

Abstract Repetitive mild traumatic brain injury (r-mTBI) has been gaining increasing attention from the researchers since several studies have reported that the cognitive dysfunctions after single mTBI become measurably long-term deficits, such as delayed speed of processing and memory dysfunction, after r-mTBI, contributing to the emerging hypothesis that r-mTBI may cause cumulative damage to the brain, and in the absence of cell death, could result in cognitive deficits which may ultimately progress to memory and learning dysfunction.

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