Moderate traumatic brain injury (TBI) in children often happen when there’s a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion.

Fluid percussion (FP) injury model is a popular animal model of traumatic brain injury (TBI), but still there are some issues need to be addressed. To increase the validity and reliability of this technique, we adapted the FP device using electromagnetic protractor, stainless-steel cylinder, changing pressure transducer position, and foam pads to adjust the parameters of FP pulse. Besides, the adjusted FP device is more automatic. The FP pulse is promptly measured and displayed in a graphic user interface software. The modified device resulted in reliable FP pulse. The accuracy of the pendulum leveling was improved with using the electromagnetic protractor with slots. We then collected behavioral, cognition, electrophysiological, and immunohistochemical data to verify the percussion effects in TBI mice. Lateral fluid percussion injury (FPI) or sham treatment was administered at the right frontal motorsensory region of male C57BL/6J mice. TBI mice showed evident motor, cognitive, and functional impairments, characterized by evaluation of neurological, righting, geotaxis and cliff aversion reflexes, limb asymmetrical use, rotarod running, and Morris water maze testing. The neurobehavioral damages were scaled with histopathological findings. Further, the overall firing rates and theta powers in hippocampal CA1 were significantly reduced in TBI mice compared to sham mice at Days 2 and 3 after electrode implanting. The adapted device induced effects on behavior and biology in mice that agree with existing models. These findings confirmed the validity of adjustments, and the modified device may boost the interest in TBI studies.

Mild traumatic brain injury (mTBI) is a clinically highly heterogeneous neurological disorder, none of the existing animal models can replicate the entire sequelae. This study aimed to develop a modified closed head injury (CHI) model of repeated mTBI (rmTBI) for investigating Ca2+ fluctuations of the affected neural network, the alternations of electrophysiology, and behavioral dysfunctions. The transcranial Ca2+ study protocol includes AAV‐GCaMP6s infection in the right motor cortex, thinned‐skull preparation, and two‐photon laser scanning microscopy (TPLSM) imaging. The CHI rmTBI model is fabricated using the thinned‐skull site and applying 2.0 atm fluid percussion with 48‐h interval. The neurological dysfunction, minor motor performance, evident mood, spatial working, and reference deficits we found in this study mimic the clinically relevant syndromes after mTBI. Besides, our study revealed that there was a trend of transition from Ca2+ singlepeak to multipeak and plateau, and the total Ca2+ activities of multipeaks and plateaus (p < .001 vs. pre‐rmTBI value) were significantly increased in ipsilateral layer 2/3 motor neurons after rm TBI. In parallel, there is a low‐frequency power shift from delta to theta band (p < .01 vs. control) in the ipsilateral layer 2/3 of motor cortex of the rmTBI mice, and the overall firing rates significantly increased (p < .01 vs. control). Moreover, rmTBI causes slight cortical and hippocampal neuron damage and possibly induces neurogenesis in the dentate gyrus (DG). The alternations of Ca2+ and electrophysiological characteristics in layer 2/3 neuronal network, histopathological changes, and possible neurogenesis may play concertedly and partially contribute to the functional outcome post‐rmTBI.