TY - JOUR
T1 - A Novel Laser-Based Zebrafish Model for Studying Traumatic Brain Injury and Its Molecular Targets
AU - Tikhonova, Maria A.
AU - Maslov, Nikolai A.
AU - Bashirzade, Alim A.
AU - Nehoroshev, Eugenyi V.
AU - Babchenko, Vladislav Y.
AU - Chizhova, Nadezhda D.
AU - Tsibulskaya, Elena O.
AU - Akopyan, Anna A.
AU - Markova, Evgeniya V.
AU - Yang, Yi Ling
AU - Lu, Kwok Tung
AU - Kalueff, Allan V.
AU - Aftanas, Lyubomir I.
AU - Amstislavskaya, Tamara G.
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - Traumatic brain injury (TBI) is a major public health problem. Here, we developed a novel model of non-invasive TBI induced by laser irradiation in the telencephalon of adult zebrafish (Danio rerio) and assessed their behavior and neuromorphology to validate the model and evaluate potential targets for neuroreparative treatment. Overall, TBI induced hypolocomotion and anxiety-like behavior in the novel tank test, strikingly recapitulating responses in mammalian TBI models, hence supporting the face validity of our model. NeuN-positive cell staining was markedly reduced one day, but not seven days, after TBI, suggesting increased neuronal damage immediately after the injury, and its fast recovery. The brain-derived neurotrophic factor (Bdnf) level in the brain dropped immediately after the trauma, but fully recovered seven days later. A marker of microglial activation, Iba1, was elevated in the TBI brain, albeit decreasing from Day 3. The levels of hypoxia-inducible factor 1-alpha (Hif1a) increased 30 min after the injury, and recovered by Day 7, further supporting the construct validity of the model. Collectively, these findings suggest that our model of laser-induced brain injury in zebrafish reproduces mild TBI and can be a useful tool for TBI research and preclinical neuroprotective drug screening.
AB - Traumatic brain injury (TBI) is a major public health problem. Here, we developed a novel model of non-invasive TBI induced by laser irradiation in the telencephalon of adult zebrafish (Danio rerio) and assessed their behavior and neuromorphology to validate the model and evaluate potential targets for neuroreparative treatment. Overall, TBI induced hypolocomotion and anxiety-like behavior in the novel tank test, strikingly recapitulating responses in mammalian TBI models, hence supporting the face validity of our model. NeuN-positive cell staining was markedly reduced one day, but not seven days, after TBI, suggesting increased neuronal damage immediately after the injury, and its fast recovery. The brain-derived neurotrophic factor (Bdnf) level in the brain dropped immediately after the trauma, but fully recovered seven days later. A marker of microglial activation, Iba1, was elevated in the TBI brain, albeit decreasing from Day 3. The levels of hypoxia-inducible factor 1-alpha (Hif1a) increased 30 min after the injury, and recovered by Day 7, further supporting the construct validity of the model. Collectively, these findings suggest that our model of laser-induced brain injury in zebrafish reproduces mild TBI and can be a useful tool for TBI research and preclinical neuroprotective drug screening.
KW - animal model
KW - behavior
KW - laser
KW - neurodegeneration
KW - neuroinflammation
KW - neurorepair
KW - traumatic brain injury
KW - zebrafish
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UR - http://www.scopus.com/inward/citedby.url?scp=85137388324&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14081751
DO - 10.3390/pharmaceutics14081751
M3 - Article
AN - SCOPUS:85137388324
SN - 1999-4923
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 8
M1 - 1751
ER -
