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. 2015 Sep;18(9):867-72.

Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

Abdolreza Babaee  1 , Seyed Hassan Eftekhar-Vaghefi  1 , Majid Asadi-Shekaari  2 , Nader Shahrokhi  3 , Samereh Dehghani Soltani  1 , Reza Malekpour-Afshar  4 , Mohsen Basiri  2
Affiliations

Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

Abdolreza Babaee et al. Iran J Basic Med Sci. 2015 Sep.

Abstract

Objectives: Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis) in several models of brain injury. Secondary injury following the primary traumatic brain injury (TBI) results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis), as well as inhibition of apoptosis in brain tissue of male rats after TBI.

Materials and methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline) and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg). All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP) marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively.

Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P<0.05) in melatonin- treated groups (no dose dependent) compared to the vehicle group. Furthermore, based on TUNEL results, melatonin treatment considerably reduced the number of apoptotic cells (P<0.05).

Conclusion: In total, the present findings suggest that melatonin treatment following TBI diminishes astrocyte reactivity and neuronal cells apoptosis in brain cortex in the rat model.

Keywords: Apoptosis; Astrogliosis; GFAP; Melatonin; Traumatic brain injury.

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Figures

Figure 1
Figure 1
Melatonin treatment reduced apoptosis of neurons induced by TBI. Results are expressed as mean±SEM and data were analyzed by one-way ANOVA followed by Tukey Kramer multiple comparisons test * Significantly different from the vehicle group (P<0.05) ## Significantly different from the vehicle group (P<0.01)
Figure 2
Figure 2
Immunohistochemical analysis of TUNEL in brain cortex of rat. Arrows show the apoptotic cells. Bar=10 µm
Figure 3
Figure 3
Melatonin treatment reduced the number of glial fibrillary acidic protein (GFAP) positive astrocytes. Results are expressed as mean±SEM, and data were analyzed by One-way ANOVA followed by Tukey-Kramer multiple comparisons test *Significantly different from the vehicle group (P<0.05) ## Significantly different from the vehicle group (P<0.01)
Figure 4
Figure 4
Immunohistochemical analysis of glial fibrillary acidic protein (GFAP) positive cells in brain cortex of rat. Arrows show the GFAP positive cells. Bar=10 µm
See this image and copyright information in PMC

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