Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

Abstract

Traumatic brain injury (TBI) is a major cause of disability worldwide. Additionally, many TBI patients are intoxicated with alcohol at the time of injury, but the impact of acute intoxication on recovery from brain injury is not well understood. We have previously found that binge alcohol prior to TBI impairs spontaneous functional sensorimotor recovery. However, whether alcohol administration in this setting affects reactive neurogenesis after TBI is not known. This study therefore sought to determine the short and long term effects of pre-TBI binge alcohol on neural precursor cell responses in the subventricular zone (SVZ) following brain injury in male rats. We found that TBI alone significantly increased proliferation in the SVZ as early as 24 hours after injury. Surprisingly, binge alcohol alone also significantly increased proliferation in the SVZ after 24 hours. However, a combined binge alcohol and TBI regimen resulted in decreased TBI-induced proliferation in the SVZ at 24 hours and 1 week post-TBI. Furthermore, at 6 weeks after TBI, binge alcohol administered at the time of TBI significantly decreased the TBI-induced neuroblast response in the SVZ and the rostral migratory stream (RMS). The results from this study suggest that pre-TBI binge alcohol negatively impacts reparative processes in the brain by decreasing short-term neural precursor cell proliferative responses as well as long-term neuroblasts in the SVZ and RMS.

Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats

“…Animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Edward Hines Jr. Veterans Affairs Hospital (permit #H13-001). Brain tissue sections encompassing the dorsal dentate gyrus from rats used in our previous study 19 were utilized in the current study. Therefore, all animal procedures, including alcohol administration, controlled cortical impact, measurement of blood alcohol level, bromodeoxyuridine (BrdU) administration, perfusion, tissue processing, and histology were performed identically as our previous study.…”

“…We administered alcohol to rats by gastric gavage for 3 consecutive days as described in our previous study, 19 (3 g/kg/dose/day at 9 AM, i.g. using Everclear (Luxco, St. Louis, MO) diluted to 40% alcohol by volume (ABV) with distilled water).…”

“…One hour following the last alcohol administration, CCI procedure was performed as described in our previous studies. 14,19 Rats were anesthetized (5% isoflurane (75 mg/ml) in 100% oxygen at induction, then 2%-3% to maintain anesthesia), and placed in a stereotaxic frame, with a skin incision and trephination (5 mm diameter) performed directly above the right forelimb area of the sensorimotor cortex (1 mm anterior, 1.5 mm lateral from bregma) 25 (see Figure 1). CCI parameters were as follow: 3 mm diameter, 2.5 m/s velocity, 2 mm depth, 250 ms dwell time (Impact One, MyNeurolab, St. Louis, MO).…”

“…Preparation of BrdU solution (20 mg/ml in sterile saline) and injection schedule were performed identically to our previous study. 19 All rats received BrdU at 100 mg/kg (i.p.) dose immediately following surgery (sham or CCI).…”

“…[15][16][17][18] Subsequently, we showed that binge alcohol decreased TBI-induced subventricular zone (SVZ) cell proliferation, attenuated SVZ neuronal differentiation, and decreased the number of newborn migratory neurons to the olfactory bulbs. 19 Neurogenesis is thought to be a compensatory mechanism observed to be up-regulated in the hippocampal dentate Neuroscience Insights gyrus (DG) 20 and the SVZ 21 after a TBI. These newly produced neurons have been associated with recovery of function following brain injuries.…”