Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats

• Published in: Hormones and behavior Vol. 64; no. 3; pp. 527 - 538
• Main Authors: Tang, Huiling, Hua, Fang, Wang, Jun, Sayeed, Iqbal, Wang, Xiaojing, Chen, Zhengjia, Yousuf, Seema, Atif, Fahim, Stein, Donald G.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.08.2013; Elsevier; Elsevier BV
• Subjects: Adult and adolescent clinical studies; Aging; Aging - drug effects; Aging - physiology; Animal cognition; Animal memory; Animals; Behavioral psychophysiology; Biological and medical sciences; Brain damage; Brain Injuries - complications; Brain Injuries - drug therapy; Combination treatments; Cytoprotection - drug effects; Disease Models, Animal; Drug Evaluation, Preclinical; Drug therapy; Functional repair; Fundamental and applied biological sciences. Psychology; Hormones and behavior; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Maze Learning - drug effects; Medical sciences; Neuroprotective Agents - administration & dosage; Organic mental disorders. Neuropsychology; Progesterone; Progesterone - administration & dosage; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Rodents; Swimming; Traumas. Diseases due to physical agents; Traumatic brain injury; Vitamin D; Vitamin D - administration & dosage; Vitamin D deficiency; Vitamin D Deficiency - complications; Vitamin D Deficiency - drug therapy; Vitamin D3 hormone; Vitamin D deficiency; Traumatic brain injury; Functional repair; Vitamin D3 hormone; Aging; Progesterone; Combination treatments; Senescence; Rat; Progestagen; Vitamin D; Adult; Repair; Nutritional status; Human; Nervous system diseases; Rodentia; Nutrition disorder; Ovarian hormone; Micronutrient; Vertebrata; Mammalia; Animal; Combined treatment; Head trauma; Sex steroid hormone
• ISSN: 0018-506X; 1095-6867; 1095-6867
• DOI: 10.1016/j.yhbeh.2013.06.009

Progesterone (PROG) and vitamin D hormone (VDH) have both shown promise in treating traumatic brain injury (TBI). Both modulate apoptosis, inflammation, oxidative stress, and excitotoxicity. We investigated whether 21days of VDH deficiency would alter cognitive behavior after TBI and whether combined PROG and VDH would improve behavioral and morphological outcomes more than either hormone alone in VDH-deficient middle-aged rats given bilateral contusions of the medial frontal cortex. PROG (16mg/kg) and VDH (5μg/kg) were injected intraperitoneally 1h post-injury. Eight additional doses of PROG were injected subcutaneously over 7days post-injury. VDH deficiency itself did not significantly reduce baseline behavioral functions or aggravate impaired cognitive outcomes. Combination therapy showed moderate improvement in preserving spatial and reference memory but was not significantly better than PROG monotherapy. However, combination therapy significantly reduced neuronal loss and the proliferation of reactive astrocytes, and showed better efficacy compared to VDH or PROG alone in preventing MAP-2 degradation. VDH+PROG combination therapy may attenuate some of the potential long-term, subtle, pathophysiological consequences of brain injury in older subjects. •TBI causes a cascade of systemic toxic events in the brain and throughout the body.•Drugs acting on multiple genomic and metabolic pathways could solve this problem.•Combined progesterone+VDH therapy improved spatial and reference memory after TBI.•Progesterone+VDH therapy reduced reactive astrocyte proliferation and neuron loss.