Minocycline Inhibits Glial Scar Formation Through CNTF Expression and Ameliorates Cognitive Impairment in Traumatic Brain Injury Rats

Authors

  • Donny Wisnu Wardhana octoral Program in Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Jawa Timur 65145, Indonesia
  • Husnul Khotimah Departement of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Jawa Timur 65145, Indonesia
  • Tommy Alfandy Nazwar Departement of Surgery, Faculty of Medicine, Universitas Brawijaya/ Saiful Anwar General Hospital, Jawa Timur 65112, Indonesia
  • Nurdiana Departement of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Jawa Timur 65145, Indonesia

DOI:

https://doi.org/10.48048/tis.2024.7945

Keywords:

CNTF, Cognitive impairment, Glial scar, Minocycline, Rats, Traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a chronic condition that causes permanent disability, particularly cognitive impairment resulting from glial scar formation. Minocycline treatment inhibits glial scar formation through the Ciliary Neurotropic Factor (CNTF) pathway in multiple sclerosis. We hypothesized that minocycline could also inhibit CNTF, which would play a role in the inhibition of glial scar formation in TBI. The objective was to evaluate the role of minocycline in inhibiting glial scar formation through the CNTF signaling pathway and ameliorating cognitive impairment in TBI model rats. Male Sprague Dawley rats (n = 16) were divided into 4 groups (n = 4/group). TBI through the weight drop model is performed on day 0, followed by minocycline treatment of 25 mg/kg (MNO1 group), 50 mg/kg (MNO2 group) and 100 mg/kg (MNO3 group) given for 14 days. The NOR test is performed on day 15, followed by immunofluorescence double staining on day 16. Minocycline plays a role in inhibiting glial scar formation in TBI model rats. Minocycline inhibits the formation of CNTF with an effect proportion of 66.3 %, which plays a role in inhibiting glial scar in the perilesional area in TBI model rats. Inhibition of glial scar improves cognitive function impairment in TBI model rats. Administration of minocycline improves cognitive function in TBI model rats with an effect proportion of 46.7 %. It can be concluded that minocycline inhibits glial scar through the inhibition of CNTF expression and ameliorates cognitive impairment in a rat model of TBI.

HIGHLIGHTS

  • Minocycline shown to inhibit CNTF formation in TBI model rats
  • CNTF inhibition can inhibit the formation of glial scar in TBI model rats.
  • Inhibition of glial scar formation can improve cognitive function impairment in TBI model rats.
  • Minocycline administration can improve cognitive function through the NOR test.

GRAPHICAL ABSTRACT

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Published

2024-08-10