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Updated: Aug 11, 2026
Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury
Published on: August 16, 2019
Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction
R O Sanchez Mejia1, V O Ona, M Li
1Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Objective:
Caspase-1 plays an important functional role mediating neuronal cell death and dysfunction after experimental traumatic brain injury (TBI) in mice. Minocycline, a derivative of the antibiotic tetracycline, inhibits caspase-1 expression. This study investigates whether minocycline can ameliorate TBI-mediated injury in mice.
Methods:
Brains from mice subjected to traumatic brain injury underwent immunohistochemical analyses for caspase-1, caspase-3, and a neuronal specific marker (NeuN). Minocycline- and saline-treated mice subjected to traumatic brain injury were compared with respect to neurological function, lesion volume, and interleukin-1beta production.
Results:
Immunohistochemical analysis revealed that activated caspase-1 and caspase-3 are present in neurons 24 hours after TBI. Intraperitoneal administration of minocycline 12 hours before or 30 minutes after TBI in mice resulted in improved neurological function when compared with mice given saline control, as assessed by Rotarod performance 1 to 4 days after TBI. The lesion volume, assessed 4 days after trauma, was significantly decreased in mice treated with minocycline before or after trauma when compared with saline-treated mice. Caspase-1 activity, quantified by measuring mature interleukin-1beta production by enzyme-linked immunosorbent assay, was considerably increased in mice that underwent TBI, and this increase was significantly diminished in minocycline-treated mice.
Conclusion:
We show for the first time that caspase-1 and caspase-3 activities localize specifically within neurons after experimental brain trauma. Further, these results indicate that minocycline is an effective pharmacological agent for reducing tissue injury and neurological deficits that result from experimental TBI, likely through a caspase-1-dependent mechanism. These results provide an experimental rationale for the evaluation of minocycline in human trauma patients.
Insights
Minocycline treatment improved neurological function and reduced brain injury in mice after traumatic brain injury (TBI). This suggests minocycline may be a potential therapy for TBI by inhibiting caspase-1 activity.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Traumatic brain injury (TBI) causes neuronal death and dysfunction.
- Caspase-1 is implicated in TBI-induced neuronal damage.
- Minocycline inhibits caspase-1 expression.
Purpose of the Study:
- To investigate the efficacy of minocycline in ameliorating TBI-mediated injury in a mouse model.
- To determine if minocycline affects caspase-1 and caspase-3 activity in neurons post-TBI.
Main Methods:
- Immunohistochemistry was used to detect caspase-1, caspase-3, and NeuN in mouse brains post-TBI.
- Neurological function, lesion volume, and interleukin-1beta production were compared between minocycline- and saline-treated mice.
Main Results:
- Activated caspase-1 and caspase-3 were found in neurons 24 hours after TBI.
- Minocycline administration improved neurological function and reduced lesion volume.
- Minocycline significantly reduced caspase-1 activity, indicated by lower interleukin-1beta levels.
Conclusions:
- Caspase-1 and caspase-3 are present in neurons following experimental brain trauma.
- Minocycline effectively reduces TBI-induced tissue injury and neurological deficits.
- Minocycline shows promise as a therapeutic agent for TBI patients, potentially via caspase-1 inhibition.
