Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ∼1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5 g/kg+0.3 g/kg/h for 15 h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (∼1.4 J, ∼30 ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6 h and 24 h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6 h, which was resolved at 24 h. AAI did not modulate the inflammatory response at 6 h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-α, and MCP-1 expression) at 24 h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI.

Long-Lasting Suppression of Acoustic Startle Response after Mild Traumatic Brain Injury

“…In other studies, spontaneous righting reflex without sensory stimulation is assessed. For the present study, spontaneous righting latencies are most relevant and these range from 4.0 to 11.5 min for mild injuries 29,30 and from 15 to 30 min for moderate-tosevere injuries. 29 By all of these measures, the brain injury in the present study would be considered mild severity (Table 2).…”

“…A wide range of peak pressures (14.7-38.9 psi) has been considered mild severity in the literature. [27][28][29][30] Because peak pressure may not reliably translate to injury severity, we also evaluated duration of apnea and righting reflex, although these measures are not often reported. In studies that described injuryinduced apnea, apnea duration for mTBI ranged from 7 to 17 sec, whereas moderate injuries resulted in apnea durations of approximately 30 sec.…”

“…In studies that described injuryinduced apnea, apnea duration for mTBI ranged from 7 to 17 sec, whereas moderate injuries resulted in apnea durations of approximately 30 sec. 28,30 Some investigators have suggested that injury severity is best assessed through righting reflex. 28 Righting latency, though, is highly dependent on the manner in which they are assessed.…”

“…ASR sensitivity was suppressed by mTBI, as demonstrated by a significant main effect of injury (F (1,30) = 15.48; p < 0.001) and significant injury · session interaction (F (1,30) = 9.07; p = 0.005). Neither main effect of experiment nor interactions involving experiment were significant.…”

Endocannabinoid Degradation Inhibition Improves Neurobehavioral Function, Blood–Brain Barrier Integrity, and Neuroinflammation following Mild Traumatic Brain Injury

“…40 All animals were exposed to all tasks, trained, and evaluated before TBI using the testing parameters that were adapted from previously published methods of assessing cognition and behavior. 39,41 To reduce any impact on behavior assessments potentially caused by the process of relocation, they were transported to the test room 1 h in advance of the start of testing.…”