Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences

Abstract

Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left. However, injury to either hemisphere resulted in probe trial deficits. In the MWM reversal task, left-right performance deficits were not evident, though left lateral injury produced mild acquisition and probe trial deficits compared to sham controls. Additionally, left and right injury produced similar neurological motor task deficits, impaired righting times, and lesion volumes. Injury to either hemisphere also produced robust ipsilateral, and modest contralateral, morphological changes in reactive microglia and astrocytes. In conclusion, left and right lateral TBI impaired MWM performance, with mild fixed platform acquisition rate differences, despite similar motor deficits, histological damage, and glial cell reactivity. Thus, while both left and right lateral TBI produce cognitive deficits, laterality in mouse MWM learning and memory merits consideration in the investigation of TBI-induced cognitive consequences.

Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury

“…After skin closure, anesthesia was discontinued and animals were placed in a heated cage until recovered and ambulatory. As we were interested in studying the impact of IL-1 on moderate to severe traumatic brain injury, mice were included only if righting reflex was >5 min ( Thompson et al, 2005 ; Fenn et al, 2015 ; Schurman et al, 2017 ). Across all studies, the average righting time ± SEM was 8.27 ± 0.21 min, which corresponded to an average peak pressure delivered of 1.32 ± 0.01 ATM.…”

Mild traumatic brain injury induces transient, sequential increases in proliferation, neuroblasts/immature neurons, and cell survival: a time course study in the male mouse dentate gyrus

“…The next time point, 7 dpi, was also selected due to it being consistently examined for TBI-induced changes in electrophysiology and behavior (Santhakumar et al, 2000(Santhakumar et al, , 2001Schurman et al, 2017;Zhang et al, 2018) . Indeed, the same LFPI parameters used here have been shown to result in DG hyperexcitability and deficits in DG-based cognition 7 dpi (Smith et al, 2012;Folweiler et al, 2018;Paterno et al, 2018) , implying that hippocampal circuitry is disrupted in this mTBI model 7 dpi.…”

Peripheral Immune Response Following Traumatic Brain Injury

“…Fluid percussion injury is performed using the injection of fluid into the cranial cavity, generating injury as a pressure wave spreads through the fluid applied to the brain [8,22]. This model results in cortical contusion, hemorrhage, inflammation, diffuse axonal injury, and gliosis, with accompanying memory and motor deficits [21,23,24]. Application of FPI causes both focal and diffuse damage to the brain and has been used to assess multiple prospective TBI therapeutics [25].…”