Akademik Veri Yönetim Sistemi
EXPERIMENTAL NEUROLOGY, cilt.357, sa.1, ss.1-13, 2022 (SCI-Expanded)
Traumatic brain injury (TBI) is an overlooked cause of morbidity, which was shown to accelerate inflammation,
oxidative stress, and neuronal cell loss and is associated with spatial learning and memory impairments and some
psychiatric disturbances in older adults. However, there is no effective treatment in order to offer a favorable
outcome encompassing a good recovery after TBI in older adults. Hence, the present study aimed to investigate
the histological and neurobehavioral effects of Allopurinol (ALL) in older rats that received repeated TBI (rTBI).
For this purpose, a weight-drop rTBI model was used on old male Wistar rats. Rats received 5 repeated TBI/sham
injuries 24 h apart and were treated with saline or Allopurinol 100 mg/kg, i.p. each time. They were randomly
assigned to three groups: control group (no injury); rTBI group (received 5 rTBI and treated with saline);
rTBI+ALL group (received 5 rTBI and treated with Allopurinol). Then, half of the animals from each group were
sacrificed on day 6 and the remaining animals were assessed with Open field, Elevated plus maze and Morris
Water Maze test. Basic neurological tasks were evaluated with neurological assessment protocol every other day
until after the 19th day from the last injury. Brain sections were processed for neuronal cell count in the hip-
pocampus (CA1), dentate gyrus (DG), and prefrontal cortex (PC). Also, an immunohistochemical assay was
performed to determine NeuN, iNOS, and TNFα levels in the brain regions. The number of neurons was markedly
reduced in CA1, GD, and PC in rats receiving saline compared to those receiving allopurinol treatment.
Immunohistochemical analysis showed marked induction of iNOS and TNFα expression in the brain tissues which
were reduced after allopurinol at 6 and 19 days post-injury. Also, ALL-treated rats demonstrated a remarkable
induce in NeuN expression, indicating a reduction in rTBI-induced neuronal cell death. In neurobehavioral an-
alyses, time spent in closed arms, in the corner of the open field, swimming latency, and distance were impaired
in injured rats; however, all of them were significantly improved by allopurinol therapy.
To sum up, this study demonstrated that ALL may mitigate rTBI-induced damage in aged rats, which suggests
ALL as a potential therapeutic strategy for the treatment of recurrent TBI.