PMID- 28245954 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 0928-4680 (Print) IS - 0928-4680 (Linking) VI - 24 IP - 2 DP - 2017 Jun TI - Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson's disease in rats. PG - 71-79 LID - S0928-4680(16)30079-7 [pii] LID - 10.1016/j.pathophys.2017.02.001 [doi] AB - 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 NFkappaB, TNF-alpha and IL-1beta 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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Kaur, Baninder AU - Kaur B AD - Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India. FAU - Prakash, Atish AU - Prakash A AD - Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India; Division of CNS Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: aprakas6@jhmi.edu. LA - eng PT - Journal Article DEP - 20170210 PL - Switzerland TA - Pathophysiology JT - Pathophysiology : the official journal of the International Society for Pathophysiology JID - 9433813 OTO - NOTNLM OT - BDNF OT - Ceftriaxone OT - Dihydrokainate OT - Glutamate OT - MPTP OT - Memantine OT - Parkinson disease EDAT- 2017/03/02 06:00 MHDA- 2017/03/02 06:01 CRDT- 2017/03/02 06:00 PHST- 2016/11/01 00:00 [received] PHST- 2017/01/31 00:00 [revised] PHST- 2017/02/03 00:00 [accepted] PHST- 2017/03/02 06:00 [pubmed] PHST- 2017/03/02 06:01 [medline] PHST- 2017/03/02 06:00 [entrez] AID - S0928-4680(16)30079-7 [pii] AID - 10.1016/j.pathophys.2017.02.001 [doi] PST - ppublish SO - Pathophysiology. 2017 Jun;24(2):71-79. doi: 10.1016/j.pathophys.2017.02.001. Epub 2017 Feb 10.