Investigating the Impact of Turmeric on Neuroinflammation and Degenerative Changes in Repetitive Traumatic Brain Injuries: Insights from Murine Model

Abstract

Objective: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Preclinical and clinical studies investigating the effects of curcumin on TBI indicate that curcumin can modulate essential signaling pathways and molecules that mediate neuroinflammation in TBI. This study aimed to explore the effects of turmeric on neuroinflammation and neurodegenerative disorder following repetitive traumatic brain injuries (rTBIs) in a rat model.

Methods: Sixty male Rattus norvegicus were housed in a controlled environment. A modified Marmarou weight drop model was used. Turmeric extract was administered once daily in the morning. The avidin-biotin-peroxidase complex technique was used to evaluate the expression of all markers. Following incubation with normal rabbit serum, the slides were subsequently incubated with monoclonal antibodies targeting tau protein (AT-8), TAR DNA-binding protein 43 (TDP-43), glial fibrillary acidic protein (GFAP), and tumor necrosis factor (TNF)-α.

Results: rTBI significantly increased the levels of inflammatory markers, such as TNF-α and GFAP. A substantial decrease of TNF-α expression was observed in the treatment group. A distinct trend was observed for GFAP expression, which was markedly decreased after the rest period compared to that in the trauma group. Phosphorylated tau expression decreased in both the treatment and pretreatment groups relative to that in the trauma and rest groups. TDP-43 expression was also significantly decreased in the treatment and pretreatment groups.

Conclusion: In conclusion, Turmeric demonstrates significant potential as a neuroprotective and anti-inflammatory agent in rTBI, especially when used as a preventive measure. Our findings challenge the significance of rest in concussion management.

Keywords: Neurodegenerative disorder; Neuroinflammation; Neuroprotective agent; Traumatic brain injury; Turmeric.

FIGURE 1. Model of mild repetitive traumatic brain injury adopted in the study.

FIGURE 2. Immunohistochemical study in control and experimental groups revealing pTau, TDP-43, GFAP, and TNF-α expression.

pTau: phosphorylated tau, TDP-43: TAR DNA-binding protein 43, GFAP: glial fibrillary acidic protein, TNF: tumor necrosis factor.

FIGURE 3. Post-hoc test visualization. Comparing TNF-α (A), GFAP (B), pTau (C), and TDP-43 (D) in all groups.

TNF: tumor necrosis factor, GFAP: glial fibrillary acidic protein, pTau: phosphorylated tau, TDP-43: TAR DNA-binding protein 43. ^**p<0.01, ^***p<0.001.

FIGURE 4. Flow diagram describing curcumin pharmacodynamics in reducing neuroinflammation and enhancing neuroprotective effects.

DHA: docosahexaenoic acid, rTBI: repetitive traumatic brain injury, NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells, Nrf2: nuclear factor erythroid 2 related factor 2, ARE: antioxidant responsive element, TNF: tumor necrosis factor, IL: interleukin, CDK5: cyclin-dependent kinase 5, p38MAPK: p38 mitogen-activated protein kinase, CaMKIIα: calcium/calmodulin-dependent protein kinase type IIα, TDP-43: TAR DNA-binding protein 43, pTau: phosphorylated tau.