Work

Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson’s disease in rats

Year: 2017

Type: article

Abstract: The present study is designed to investigate the role of glutamate transporter in neuroprotection of ceftriaxone against MPTP induced PD animal model. Young male Wistar rats were subjected to intra-nigral administration of MPTP for the induction of Parkinson's disease. Glutamate modulators like ceftriaxone (CFX), Memantine (MEM) and Dihydrokainate (DHK) were administered to MPTP-lesioned rats. Different behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical parameters were measured. Intranigral administration of MPTP showed significant impairment of motor behavior and marked increase in inflammatory mediators and oxidative stress parameters in rats. In addition, MPTP also produced significant decrease in brain-derived neurotrophic factor (BDNF) in striatum of rats. However, chronic administration of ceftriaxone (200mg/kg) has shown significant improvement in motor behavioral deficits and oxidative damage. In addition, Ceftriaxone also attenuated the marked increase of NFκB, TNF-α and IL-1β in MPTP treated rats thus, conferring its neuro-inflammatory property. Further, Ceftriaxone significantly restored the decreased activity of BDNF in striatum of MPTP treated rats. Moreover, pre-treatment of memantine (20mg/kg) with sub-therapeutic dose of ceftriaxone (100mg/kg) potentiated the protective effect of ceftriaxone. Furthermore, intra-nigral injection of DHK (200 nmol) with lower dose of ceftriaxone (100mg/kg) reversed the protective effect of ceftriaxone in MPTP treated rats. The present study concluded that ceftriaxone produce beneficial effect against MPTP induced PD like symptoms rats through glutamatergic pathways.

Source: Pathophysiology

DOI: 10.1016/j.pathophys.2017.02.001

Authors: Baninder Kaur, Atish Prakash

Institutions: Indo Soviet Friendship College of Pharmacy, Johns Hopkins University, Johns Hopkins Medicine

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,689