Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

Lai, Pei Chun; Huang, Yuejiao; Wu, Chia Chen; Lai, Chun–Kit; Wang, Pen Jung; Chiu, Ted H.

doi:10.1186/1423-0127-18-69

Cited by 41 publications

(37 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This could be because of the dynamic characteristic of the CBF and the pathophysiological processes occur after arterial ligation. Our results agrees with other studies in focal ischaemic and hypoxic-ischaemic model that showed no alteration in glutamate transporter protein level 28,43,49 . Some studies showed increased uptake activity without transporter protein level changes 28 .…”

Section: Discussionsupporting

confidence: 83%

“…Among all β-lactam antibiotics studies, ceftriaxone (CTX) shows the highest potency in the upregulation of glutamate transporter 25 . The upregulation of glutamate transporter by CTX treatment was associated with the reduction of neuronal injury and neurological deficit 28,42,43 . Therefore, we applied CTX to the animals from day 1-5 after vessel ligation.…”

Section: Discussionmentioning

confidence: 99%

“…GLT-1 which is specifically expressed in astrocyte is responsible for up to 90% of glutamate uptake in the brain 48 . GLT-1 protein was measured one week after 2VO induction, during which time the peak of CTXupregulation of GLT-1 with effective dose of CTX occurs 27,43 . Our results showed that the percentages of mean hippocampal GLT-1 expression were about 186% for 2VO-CTX and 135% for 2VO-Veh compared with that of the sham.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

Koomhin¹,

Tilokskulchai²,

Tapechum

2012

ScienceAsia

View full text Add to dashboard Cite

Cerebral hypoperfusion is associated with cognitive decline in ageing, mild cognitive impairment, vascular type dementia, and Alzheimer's disease. The mechanisms leading to such neurological impairments are still uncertain. Although several mechanisms have been proposed as contributing factors leading to neuronal injury, glutamate excitotoxicity seems to be the relevant one. Recently, it was found that β-lactam antibiotics such as ceftriaxone show a neuroprotective effect by upregulation of glutamate transporter and reduction of glutamate excitotoxicity. To study the contribution of glutamate excitotoxicity and the effects of ceftriaxone on spatial learning and memory in chronic cerebral hypoperfusion, we conducted experiments in rats subjected to permanent bilateral common carotid artery occlusion. Ceftriaxone (200 mg/kg) was injected daily in rats for 5 days after the onset of the arterial ligation. A Morris water maze was used to assess learning and memory two months after arterial ligation. Hippocampal histology and glutamate transporter 1 (GLT-1) expression were also studied. Results showed that ceftriaxone improved learning and memory performance. Consistently, the histological study showed an increase hippocampal CA1 and CA3 neuronal numbers in the ceftriaxone-treated group compared with the vehicle-treated group. Although not statistically significant, the GLT-1 protein level in the hippocampus was 86% higher than the sham group. We conclude that ceftriaxone treatment can attenuate neuronal injury and improve spatial learning and memory after chronic cerebral hypoperfusion and that glutamate excitotoxicity may play an important role in the pathophysiology of chronic cerebral hypoperfusion.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

Koomhin¹,

Tilokskulchai²,

Tapechum

2012

ScienceAsia

View full text Add to dashboard Cite

show abstract

“…In addition, our finding of reduced GFAP indicates a net reduction of injury severity in the ceftriaxone-treated rats and points to a plausible neuroprotective effect, as previously suggested by data from other rodent disease models, such as stroke and ALS. 16,19 Although in support of our overall hypothesis that GLT-1 up-regulation by ceftriaxone mitigates glutamate-mediated excitotoxicity, conclusive evidence that GLT-1 restoration after TBI is causally related to reduced gliosis and reduced post-traumatic seizure counts will have to be obtained in studies beyond the scope of this report. We thus also anticipate to study whether individual GLT-1 isoforms are differentially depressed after injury and which isoform may be modulated preferentially by ceftriaxone.…”

Section: Ceftriaxone Treatment Reduces Post-traumatic Astrogliosis Anmentioning

confidence: 58%

“…14 published data showing reduced neuronal death in rodent models of hypoxic-ischemic brain injury 16,17 and behavioral improvement in a transgenic rodent model of Huntington's disease. 18 Also, in the mouse amyotrophic lateral sclerosis (ALS) model, where glutamate-mediated excitotoxicity is contributory to the mechanisms of neuronal injury, ceftriaxone also delays neuronal loss and increases mouse survival.…”

mentioning

confidence: 99%

Ceftriaxone Treatment after Traumatic Brain Injury Restores Expression of the Glutamate Transporter, GLT-1, Reduces Regional Gliosis, and Reduces Post-Traumatic Seizures in the Rat

Goodrich

Kabakov

Hameed

et al. 2013

Journal of Neurotrauma

141

View full text Add to dashboard Cite

Excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely to posttraumatic epilepsy. Glutamate transport is the only known mechanism of extracellular glutamate clearance, and glutamate transporter 1 (GLT-1) is the major glutamate transporter of the mammalian brain. We tested, by immunoblot, in the rat lateral fluid percussion injury TBI model whether GLT-1 expression is depressed in the cortex after TBI, and whether GLT-1 expression after TBI is restored after treatment with ceftriaxone, a well-tolerated b-lactam antibiotic previously shown to enhance GLT-1 expression in noninjured animals. We then tested whether treatment with ceftriaxone mitigates the associated regional astrogliosis, as reflected by glial fibrillary acid protein (GFAP) expression, and also whether ceftriaxone treatment mitigates the severity of post-traumatic epilepsy. We found that 7 days after TBI, GLT-1 expression in the ipsilesional cortex was reduced by 29% (n = 7/group; p < 0.01), relative to the contralesional cortex. However, the loss of GLT-1 expression was reversed by treatment with ceftriaxone (200 mg/kg, daily, intraperitoneally). We found that ceftriaxone treatment also decreased the level of regional GFAP expression by 43% in the lesioned cortex, relative to control treatment with saline (n = 7 per group; p < 0.05), and, 12 weeks after injury, reduced cumulative post-traumatic seizure duration (n = 6 rats in the ceftriaxone treatment group and n = 5 rats in the saline control group; p < 0.001). We cautiously conclude that our data suggest a potential role for ceftriaxone in treatment of epileptogenic TBI.

show abstract

Cerebral Palsy: Treatments and Therapeutics

Ferguson

2015

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Cerebral palsy ( CP ) is a non‐progressive motor disorder affecting approximately 3 out of every 1000 infants in the United States. Although it is classified as a motor disorder, the deficits are caused by pre‐ or neonatal brain injury. Unfortunately, there is no cure for CP and currently, symptom management is the only treatment option available. As research begins to unravel the underlying causes and cellular changes leading to CP , potential treatments and therapeutics can be investigated to prevent brain damage following insults. Today, only two therapies are approved for use in the hospital setting: hypothermia and magnesium sulphate. Both of these therapies attempt to lessen the brain damage by slowing processes of inflammation and cell death. Other potential therapies are in clinical trials to test safety and efficacy for use in humans. Some drugs have shown promise in animal models; however, they have not yet been tested in humans. Researchers are searching for a cure. Key Concepts There is no cure for cerebral palsy and currently approved treatments target the symptoms of cerebral palsy, not the underlying causes. Hypothermia and magnesium sulphate are the only two therapeutics used in the hospital setting to slow or lessen brain damage following labour and delivery complications. Therapeutics targeting the excitatory amino acid neurotransmitter glutamate, along with glutamate receptor and transporter expression and function, appear to be promising. Drug treatments targeting growth factors and endogenous proteins may be beneficial to reduce cell death leading to cerebral palsy. Because inflammation plays a role in cerebral palsy, drug treatment that reduces the inflammatory response may also reduce brain damage following insults.

show abstract

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

Cited by 41 publications

References 51 publications

Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

Ceftriaxone Treatment after Traumatic Brain Injury Restores Expression of the Glutamate Transporter, GLT-1, Reduces Regional Gliosis, and Reduces Post-Traumatic Seizures in the Rat

Cerebral Palsy: Treatments and Therapeutics

Contact Info

Product

Resources

About