Skip to main content
Top
Published in: BMC Neurology 1/2023

Open Access 01-12-2023 | Central Nervous System Trauma | Research

Modification of the height of a weight drop traumatic brain injury model that causes the formation of glial scar and cognitive impairment in rats

Authors: Donny Wisnu Wardhana, Hendy Setyo Yudhanto, Wibi Riawan, Husnul Khotimah, Happy Kurnia Permatasari, Tommy Alfandy Nazwar, Nurdiana Nurdiana

Published in: BMC Neurology | Issue 1/2023

Login to get access

Abstract

Objective

Traumatic brain injury (TBI) is a chronic, progressive condition associated with permanent disabilities, particularly cognitive impairments. Glial scar formation following TBI is considered a contributing factor to these persistent disabilities. Currently, limited research exists on pharmacological interventions targeting glial scar prevention that require a standard weight drop TBI model for glial scar formation. Since there is no established standard TBI model for glial scar formation, this study aims to validate and modify the height of the weight drop model to identify glial scar formation and cognitive impairments.

Methods

Fifteen male Sprague Dawley rats were randomly divided into sham, WD1, and WD2 groups. The weight drop model with a 10 g load was applied to the right exposed brain of the rats from a height of 5 cm (WD1) and 10 cm (WD2) using a modified Feeney’s weight drop device. Cognitive impairments were confirmed using the novel object recognition (NOR) test with ethovision software on day 15. Subsequently, the rats were decapitated on day 16, and GFAP immunohistochemical staining was performed to confirm the presence of glial scarring.

Results

The WD1 and WD2 groups exhibited a significant increase in glial scar formation compared to the sham group, with the WD2 group resulting in even more pronounced glial scar formation. Only the WD2 model caused statistically significant cognitive damage. The negative correlation coefficient indicates that an increase in GFAP + cells will decrease the cognitive function.

Conclusion

Modification of the height of the weight drop model, by dropping a weight of 10 g from a height of 10 cm (WD2 group) onto the right brain exposed of the rat has been proven to induce the formation of a glial scar and cognitive impairment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Deshetty UM, Periyasamy P. Potential biomarkers in Experimental Animal models for traumatic brain Injury. Volume 12. Journal of Clinical Medicine. MDPI; 2023. Deshetty UM, Periyasamy P. Potential biomarkers in Experimental Animal models for traumatic brain Injury. Volume 12. Journal of Clinical Medicine. MDPI; 2023.
2.
go back to reference Ma X, Aravind A, Pfister BJ, Chandra N, Haorah J. Animal models of traumatic Brain Injury and Assessment of Injury Severity. Molecular Neurobiology. Volume 56. Humana Press Inc.; 2019. pp. 5332–45. Ma X, Aravind A, Pfister BJ, Chandra N, Haorah J. Animal models of traumatic Brain Injury and Assessment of Injury Severity. Molecular Neurobiology. Volume 56. Humana Press Inc.; 2019. pp. 5332–45.
3.
go back to reference Chakraborty N, Hammamieh R, Gautam A, Miller SA, Condlin ML, Jett M et al. TBI weight-drop model with variable impact heights differentially perturbs hippocampus-cerebellum specific transcriptomic profile. Exp Neurol. 2021;335. Chakraborty N, Hammamieh R, Gautam A, Miller SA, Condlin ML, Jett M et al. TBI weight-drop model with variable impact heights differentially perturbs hippocampus-cerebellum specific transcriptomic profile. Exp Neurol. 2021;335.
4.
go back to reference Kuo CW, Chang MY, Liu HH, He XK, Chan SY, Huang YZ et al. Cortical electrical stimulation ameliorates traumatic Brain Injury-Induced Sensorimotor and Cognitive deficits in rats. Front Neural Circuits. 2021;15. Kuo CW, Chang MY, Liu HH, He XK, Chan SY, Huang YZ et al. Cortical electrical stimulation ameliorates traumatic Brain Injury-Induced Sensorimotor and Cognitive deficits in rats. Front Neural Circuits. 2021;15.
5.
go back to reference Pavlovic D, Pekic S, Stojanovic M, Popovic V. Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary. Springer New York LLC; 2019. Pavlovic D, Pekic S, Stojanovic M, Popovic V. Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary. Springer New York LLC; 2019.
6.
go back to reference Bodnar CN, Roberts KN, Higgins EK, Bachstetter AD. A systematic review of closed Head Injury models of mild traumatic brain Injury in mice and rats. Journal of Neurotrauma. Volume 36. Mary Ann Liebert Inc.; 2019. pp. 1683–706. Bodnar CN, Roberts KN, Higgins EK, Bachstetter AD. A systematic review of closed Head Injury models of mild traumatic brain Injury in mice and rats. Journal of Neurotrauma. Volume 36. Mary Ann Liebert Inc.; 2019. pp. 1683–706.
7.
go back to reference Shi X, Bai H, Wang J, Wang J, Huang L, He M, et al. Behavioral Assessment of sensory, Motor, emotion, and Cognition in Rodent models of Intracerebral Hemorrhage. Frontiers in Neurology. Volume 12. Frontiers Media S.A.; 2021. Shi X, Bai H, Wang J, Wang J, Huang L, He M, et al. Behavioral Assessment of sensory, Motor, emotion, and Cognition in Rodent models of Intracerebral Hemorrhage. Frontiers in Neurology. Volume 12. Frontiers Media S.A.; 2021.
8.
go back to reference Cooke P, Janowitz H, Dougherty SE. Neuronal Redevelopment and the Regeneration of Neuromodulatory Axons in the adult mammalian Central Nervous System. Frontiers in Cellular Neuroscience. Volume 16. Frontiers Media S.A.; 2022. Cooke P, Janowitz H, Dougherty SE. Neuronal Redevelopment and the Regeneration of Neuromodulatory Axons in the adult mammalian Central Nervous System. Frontiers in Cellular Neuroscience. Volume 16. Frontiers Media S.A.; 2022.
9.
go back to reference Leibinger M, Andreadaki A, Diekmann H, Fischer D. Neuronal STAT3 activation is essential for CNTF- and inflammatory stimulation-induced CNS axon regeneration. Cell Death Dis. 2013;4(9). Leibinger M, Andreadaki A, Diekmann H, Fischer D. Neuronal STAT3 activation is essential for CNTF- and inflammatory stimulation-induced CNS axon regeneration. Cell Death Dis. 2013;4(9).
10.
go back to reference Zhou Y, Shao A, Yao Y, Tu S, Deng Y, Zhang J. Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury. Cell Communication and Signaling. Volume 18. BioMed Central Ltd.; 2020. Zhou Y, Shao A, Yao Y, Tu S, Deng Y, Zhang J. Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury. Cell Communication and Signaling. Volume 18. BioMed Central Ltd.; 2020.
11.
12.
go back to reference Xu P, Huang X, Niu W, Yu D, Zhou M, Wang H. Metabotropic glutamate receptor 5 upregulation of γ-aminobutyric acid transporter 3 expression ameliorates cognitive impairment after traumatic brain injury in mice. Brain Res Bull. 2022;183:104–15.CrossRefPubMed Xu P, Huang X, Niu W, Yu D, Zhou M, Wang H. Metabotropic glutamate receptor 5 upregulation of γ-aminobutyric acid transporter 3 expression ameliorates cognitive impairment after traumatic brain injury in mice. Brain Res Bull. 2022;183:104–15.CrossRefPubMed
13.
go back to reference Chen H, Chan YL, Nguyen LT, Mao Y, de Rosa A, Beh IT, et al. Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations. Clin Exp Pharmacol Physiol. 2016;43(11):1107–14.CrossRefPubMed Chen H, Chan YL, Nguyen LT, Mao Y, de Rosa A, Beh IT, et al. Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations. Clin Exp Pharmacol Physiol. 2016;43(11):1107–14.CrossRefPubMed
14.
go back to reference Silver JM, McAllister, Thomas W, Yudofsky, Stuart C. Textbook of Traumatic Brain Injury. 2nd ed. Washington: American Psychiatric Association; 2014. Silver JM, McAllister, Thomas W, Yudofsky, Stuart C. Textbook of Traumatic Brain Injury. 2nd ed. Washington: American Psychiatric Association; 2014.
15.
go back to reference Qubty D, Frid K, Har-Even M, Rubovitch V, Gabizon R, Pick CG. Nano-PSO Administration attenuates cognitive and neuronal deficits resulting from traumatic brain Injury. Molecules. 2022;27(9). Qubty D, Frid K, Har-Even M, Rubovitch V, Gabizon R, Pick CG. Nano-PSO Administration attenuates cognitive and neuronal deficits resulting from traumatic brain Injury. Molecules. 2022;27(9).
16.
go back to reference Stetter C, Lopez-Caperuchipi S, Hopp-Krämer S, Bieber M, Kleinschnitz C, Sirén AL et al. Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor xii deficient mice. Int J Mol Sci. 2021;22(9). Stetter C, Lopez-Caperuchipi S, Hopp-Krämer S, Bieber M, Kleinschnitz C, Sirén AL et al. Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor xii deficient mice. Int J Mol Sci. 2021;22(9).
17.
go back to reference Sekar S, Viswas RS, Mahabadi HM, Alizadeh E, Fonge H, Taghibiglou C. Concussion/mild traumatic brain injury (Tbi) induces brain insulin resistance: a positron emission tomography (pet) scanning study. Int J Mol Sci. 2021;22(16). Sekar S, Viswas RS, Mahabadi HM, Alizadeh E, Fonge H, Taghibiglou C. Concussion/mild traumatic brain injury (Tbi) induces brain insulin resistance: a positron emission tomography (pet) scanning study. Int J Mol Sci. 2021;22(16).
18.
go back to reference Kempuraj D, Ahmed ME, Selvakumar GP, Thangavel R, Raikwar SP, Zaheer SA et al. Mast Cell Activation, Neuroinflammation, and Tight Junction Protein Derangement in Acute Traumatic Brain Injury. Mediators Inflamm. 2020;2020. Kempuraj D, Ahmed ME, Selvakumar GP, Thangavel R, Raikwar SP, Zaheer SA et al. Mast Cell Activation, Neuroinflammation, and Tight Junction Protein Derangement in Acute Traumatic Brain Injury. Mediators Inflamm. 2020;2020.
19.
go back to reference Luo Mling, Pan L, Wang L, Wang Hyan, Li S, Long Z, yun, et al. Transplantation of NSCs promotes the recovery of cognitive functions by regulating neurotransmitters in rats with traumatic brain Injury. Neurochem Res. 2019;44(12):2765–75.CrossRefPubMed Luo Mling, Pan L, Wang L, Wang Hyan, Li S, Long Z, yun, et al. Transplantation of NSCs promotes the recovery of cognitive functions by regulating neurotransmitters in rats with traumatic brain Injury. Neurochem Res. 2019;44(12):2765–75.CrossRefPubMed
Metadata
Title
Modification of the height of a weight drop traumatic brain injury model that causes the formation of glial scar and cognitive impairment in rats
Authors
Donny Wisnu Wardhana
Hendy Setyo Yudhanto
Wibi Riawan
Husnul Khotimah
Happy Kurnia Permatasari
Tommy Alfandy Nazwar
Nurdiana Nurdiana
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2023
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-023-03494-y

Other articles of this Issue 1/2023

BMC Neurology 1/2023 Go to the issue