evaluate the impact of Doxycycline on both clinical outcome and blood levels of NSE in patients with TBI.

1. Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damnhour University.
2. All Participants agreed to take part in this clinical research and provide informed consent. for unconscious participants, the informed consent was obtained from their legally authorized representative.
3. Patients with moderate to severe TBI will be enrolled from Tanta university hospitals.
4. Serum samples will be collected for measuring the biomarkers.
5. Our design is randomized, controlled study.
6. All enrolled patients will be divided into 2 groups, Group (1) 25 patients that receive doxycycline 100 mg twice daily, either orally or through a nasogastric tube for 5 days, and group (2) will be 25 patients will receive placebo in addition to the standard treatment.
7. All patients will be followed up during ICU period.
8. Statsicial tests appropriate to the study design will be conducted to evaluate the significance of the results.
9. Measuring outcome: the primary outcome is the change in the serum level of acute brain injury biomarkers.
10. Results, conclusions, discussion and recommendations will be given.

Inclusion Criteria:

1. Hospital admission in the first 24 h of injury,
2. 18 to 90 years of age and
3. Both sexes with moderate to severe traumatic brain injury (GCS score ≤ 12).
4. Able to tolerate enteral feeding and drug administration within the first 24 hours of TBI

Exclusion Criteria:

1. Hypersensitivity to tetracyclines
2. Pregnant and breast feeding women,
3. History of autoimmune disease.
4. History of receiving chronic steroid treatment and isotretinoin,
5. Pre-existing hepatic (AST, ALT greater than 3 times the upper limit of normal) or renal failure (BUN/ Creatinine 20:1; creatinine > 2 mg/dL),
6. Known malignancies