title: Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats.
abstract: 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 21 days 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 (16 mg/kg) and VDH (5 μg/kg) were injected intraperitoneally 1 h post-injury. Eight additional doses of PROG were injected subcutaneously over 7 days 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.
authors.affiliation: Department of Emergency Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Tang
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Iqbal
authors.initials: I
authors.lastname: Sayeed
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Seema
authors.initials: S
authors.lastname: Yousuf
authors.forename: Fahim
authors.initials: F
authors.lastname: Atif
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011374:Progesterone / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D014807:Vitamin D / Q000008:administration & dosage*; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy
chemical_list: D018696:Neuroprotective Agents; D014807:Vitamin D; D011374:Progesterone
keywords: Aging; Combination treatments; Functional repair; Progesterone; Traumatic brain injury; Vitamin D deficiency; Vitamin D3 hormone
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