Repeated Mild Traumatic Brain Injury: Mechanisms of Cerebral Vulnerability

Abstract

Among the 3.5 million annual new head injury cases is a subpopulation of children and young adults who experience repeated traumatic brain injury (TBI). The duration of vulnerability after a single TBI remains unknown, and biomarkers have yet to be determined. Decreases in glucose metabolism (cerebral metabolic rate of glucose [CMRglc]) are consistently observed after experimental and human TBI. In the current study, it is hypothesized that the duration of vulnerability is related to the duration of decreased CMRglc and that a single mild TBI (mTBI) increases the brain's vulnerability to a second insult for a period, during which a subsequent mTBI will worsen the outcome. Postnatal day 35 rats were given sham, single mTBI, or two mTBI at 24-h or 120-h intervals. (14)C-2-deoxy-D-glucose autoradiography was conducted at 1 or 3 days post-injury to calculate CMRglc. At 24 h after a single mTBI, CMRglc is decreased by 19% in both the parietal cortex and hippocampus, but approached sham levels by 3 days post-injury. When a second mTBI is introduced during the CMRglc depression of the first injury, the consequent CMRglc is depressed (36.5%) at 24 h and remains depressed (25%) at 3 days. In contrast, when the second mTBI is introduced after the metabolic recovery of the first injury, the consequent CMRglc depression is similar to that seen with a single injury. Results suggest that the duration of metabolic depression reflects the time-course of vulnerability to second injury in the juvenile brain and could serve as a valuable biomarker in establishing window of vulnerability guidelines.

Repeated mild traumatic brain injury: potential mechanisms of damage

“…254 Finally, pediatric populations exhibit different responses to adults experiencing a similar head trauma, 255 and limited studies have been conducted assessing younger populations. 235,236,256,257 Conclusions Long-term cognitive impairments following CNS injury and in neurodegenerative diseases have been associated with prolonged oxidative stress conditions 131,258 and impaired signal conduction along dysmyelinated axons. 259 Further, persisting behavioral deficits after TBI have been associated with progressive activation of astrocytes 260 and microglia.…”

Influences of Developmental Age on the Resolution of Diffuse Traumatic Intracranial Hemorrhage and Axonal Injury

“…38 Similarly, Prins and colleagues demonstrated that two injuries separated by 24 h were associated with a greater and more persistent decrease in cerebral metabolism than either a single injury or two injuries separated by three days in rats. 39 The evolution of secondary injury also likely depends upon the brain injury mechanism with different injury models yielding varying time dependencies. Duhaime and colleagues used a porcine controlled cortical impact model and although they also found peak lesion volumes in five-day-old piglets at one day post-injury, fourweek-old piglets had peak lesion volumes at seven days postinjury.…”

Head-Impact–Measurement Devices: A Systematic Review

“…9 This metabolic disruption lasts about a week, mirroring the timeline of clinical symptom recovery. 10,11 In animal models, researchers 12 have demonstrated that a second concussion during this period of brain vulnerability creates greater metabolic and cognitive impairment for a longer time. Similar findings of vulnerability and impaired recovery have also been shown in male athletes.…”

“…13 Removing injured athletes from participation close to the time of injury reduces the risk of secondary injury when they are vulnerable to the cumulative effect of concussions. [12][13][14] However, given underreporting, 5,7 transient symptoms, 15 delayed onset of symptoms, 16 and the few concussions occurring with loss of consciousness, concussions are often difficult to detect and diagnose. [17][18][19] Therefore, objective and quantitative diagnostic tools that are more sensitive and specific to concussive injury are needed.…”