title: Systemic sepsis exacerbates mild post-traumatic brain injury in the rat.
abstract: The development of sepsis in patient suffering from traumatic brain injury (TBI) represents a frequent complication that has been associated with worsened global and neurological outcome. In an effort to better characterize the influence of sepsis following TBI, we developed an in vivo model of combined TBI and sepsis in the rat by coupling two validated models: (1) Controlled Cortical Impact (CCI) and (2) Cecal Ligation and Puncture (CLP). Possible contributing effects of sepsis on post-traumatic outcome were evaluated as mortality rate, body weight change, neurological motor (beam balance), cognitive (Morris water maze [MWM] for memory and learning) function, histopathological damage (lesion volume, cell counts in the CA1 and CA3 hippocampal areas), and morphological indices of inflammation (activated microglia and astrocytes) for the 14-day study period. In this study, we produced a mild TBI characterized by a low mortality rate, a transient delay in weight gain, and a transient impairment in motor and cognitive functions. The histological counterpart was represented by a cortical lesion in the area of impact at 14 days post-injury, associated with cell loss in the CA1 and CA3 hippocampal regions, and scarce infiltration of microglia. The superimposition of sepsis on this mild TBI model resulted in worsening of post-injury mortality and weight loss, significant exacerbation of post-injury motor deficit and cognitive impairments, and further exacerbation of neuronal cell death in the CA3 area together with over-expression and activation of microglial cells in the peri-lesional area. Altogether, our findings indicate that sepsis, when superimposed on TBI, exerts a negative effect on the evolution of post-traumatic damage.
authors.affiliation: Critical Care Department, Section of Anesthesiology and IC, University of Florence, Firenze, Italy.
authors.forename: Luna
authors.initials: L
authors.lastname: Venturi
authors.forename: Marco
authors.initials: M
authors.lastname: Miranda
authors.forename: Valentina
authors.initials: V
authors.lastname: Selmi
authors.forename: Luca
authors.initials: L
authors.lastname: Vitali
authors.forename: Alessia
authors.initials: A
authors.lastname: Tani
authors.forename: Martina
authors.initials: M
authors.lastname: Margheri
authors.forename: Angelo Raffaele
authors.initials: AR
authors.lastname: De Gaudio
authors.forename: Chiara
authors.initials: C
authors.lastname: Adembri
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000401:mortality / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000473:pathology; D002432:Cecum / Q000293:injuries / Q000502:physiology; D002452:Cell Count; D003071:Cognition / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D017628:Microglia / Q000473:pathology; D009048:Motor Skills / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000401:mortality / Q000473:pathology*