This article discusses a study exploring the link between mild closed-head impact injuries and the onset of chronic traumatic encephalopathy (CTE), utilizing both human and animal models to delve into the mechanisms behind CTE. The research examined the brains of teenage athletes who succumbed shortly after experiencing sports-related head impacts. Findings included signs of astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology, indicating early CTE pathologies might be initiated by such injuries. Prior research suggested that the intensity of head motion plays a critical role in CTE development, more so than the type of injury. This study hypothesized that shearing forces from closed-head impacts cause a sequence of microvascular injuries and neuroinflammation, similar to effects seen in blast exposures.
To probe deeper into CTE's causal mechanisms, the researchers designed a mouse model using a compressed gas-driven system to deliver scalable closed-head impacts to conscious mice. This setup, mimicking head kinematics from earlier blast injury models, allowed for the study of immediate neurobehavioral and cellular responses without anesthesia effects. The focus was on the immediate aftermath of injury, a crucial period for understanding CTE's early development.
In mice, these injuries resulted in short-term neurobehavioral impairments reminiscent of human concussion symptoms, such as reduced arousal, responsiveness, and motor skills, which typically resolved within three hours post-injury. Early examination of mouse brains post-impact showed progressive pathologies associated with CTE, including neuronal death, astrocytosis, microgliosis, and the buildup of cis-phosphorylated tau protein (cis-p-tau), detectable as early as 24 hours after injury and persisting for over five months. These observations, coupled with evidence of traumatic microvascular damage and blood-brain barrier compromise, suggest a mechanistic link between closed-head impact injuries and CTE.
The study concludes that a series of pathologies-traumatic microvascular injury, blood-brain barrier compromise, microglial activation, perivascular neuroinflammation, myelinated axonopathy, and phosphorylated tauopathy-are integral to closed-head impact injuries. These findings underscore the possibility that even mild injuries can initiate a pathological cascade leading to early CTE signs. The study advocates for more research into the long-term effects of such injuries and the development of diagnostic and therapeutic approaches for CTE.
