Ceftriaxone pretreatment confers neuroprotection in rats with acute glaucoma and reduces the score of seizures induced by pentylenotetrazole in mice

J Biochem Mol Toxicol. 2020 Nov;34(11):e22578. doi: 10.1002/jbt.22578. Epub 2020 Jul 15.

Abstract

β-Lactam antibiotics such as ceftriaxone, are potent stimulators of the expression of l-glutamate transporter GLT-1 and may exert neuroprotective effects when chronically used in rats and mice. In this study, we used two animal models to test the neurological effect of subchronic treatment with ceftriaxone: experimental acute glaucoma in Wistar rats and induction of acute seizures with pentylenetetrazole in mice. We also assessed the performance of mice in the rotarod to calculate therapeutic indexes and exploratory activity in the open field. Our results showed that subchronic use of ceftriaxone was neuroprotective in both models, reducing injury in acute ischemia and ischemia/reperfusion in specific layers of retina and leading to a decrease in the seizure severity score. In behavioral experiments, we observed that ceftriaxone increased hyperactivity followed by a decrease in exploratory behavior in the open field, and there was no motor impairment in the rotarod test. We conclude that ceftriaxone may be useful as a tool in the development of new neuroprotective drugs targeting diseases which present a possible dysfunction in the balance of glutamatergic neurotransmission.

Keywords: ceftriaxone; glaucoma; l-glutamate; pentylenetetrazole; seizures.

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Behavior, Animal / drug effects
  • Ceftriaxone / administration & dosage*
  • Convulsants / pharmacology*
  • Glaucoma / physiopathology*
  • Male
  • Mice
  • Neuroprotective Agents / administration & dosage*
  • Rats
  • Rats, Wistar
  • Seizures / prevention & control*
  • Tetrazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Convulsants
  • Neuroprotective Agents
  • Tetrazoles
  • pentylenotetrazole
  • Ceftriaxone