The beta-lactam antibiotic, ceftriaxone, provides neuroprotective potential via anti-excitotoxicity and anti-inflammation response in a rat model of traumatic brain injury

J Trauma Acute Care Surg. 2012 Sep;73(3):654-60. doi: 10.1097/TA.0b013e31825133c0.


Background: The beta-lactam antibiotic, ceftriaxone (CTX), has been reported to induce neuroprotection in animal models of diverse neurologic diseases. Currently, no data have explored the potential for CTX to provide neuroprotection in the animal models of traumatic brain injury (TBI). The aim of this study was to investigate the neuroprotective effect by CTX on TBI and to determine the underlying mechanisms.

Methods: Rats were immediately subjected to a lateral cortical impact injury caused by a free-falling object and divided randomly into three groups: sham-operated, trauma, and trauma + CTX treatment group. The CTX treatment group was given CTX (200 mg/kg of body weight, intravenously) immediately after injury. The cognitive function was assessed by Y-maze testing and cerebral edema was evaluated. Inflammatory cytokines expression was measured using enzyme-linked immunosorbent assay array. The expression of glutamate transporter-1 protein was identified by Western blot analysis.

Results: This study shows that the CTX causes attenuation of TBI-induced cerebral edema and cognitive function deficits. CTX treatment significantly reduced levels of the proinflammatory cytokines interleukin-1[beta], interferon-[gamma], and tumor necrosis factor-[alpha] and up-regulated glutamate transporter-1 expression after TBI.

Conclusion: Our results provide in vivo evidence that CTX could exert neuroprotective effect against TBI by improving cognitive function and alleviating brain edema via reducing excitotoxicity and inflammation after TBI.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Biopsy, Needle
  • Blotting, Western
  • Brain Edema / drug therapy*
  • Brain Edema / mortality
  • Brain Edema / pathology
  • Brain Edema / prevention & control
  • Brain Injuries / drug therapy*
  • Brain Injuries / mortality
  • Brain Injuries / pathology
  • Ceftriaxone / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Excitatory Amino Acid Transporter 2 / genetics*
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Immunohistochemistry
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Survival Rate
  • Treatment Outcome
  • Up-Regulation
  • beta-Lactams / pharmacology*


  • Cytokines
  • Excitatory Amino Acid Transporter 2
  • Neuroprotective Agents
  • Slc1a2 protein, rat
  • beta-Lactams
  • Ceftriaxone