Santana-Gomez Cesar, Smith Gregory, Mousavi Ava, Shamas Mohamad, Harris Neil G, Staba Richard
bioRxiv. 2024 Jul 2:2024.06.28.601257. doi: 10.1101/2024.06.28.601257.
Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.
创伤性脑损伤（TBI）是全球发病和死亡的主要原因。人们已经开发了多种损伤模型来研究这种神经系统疾病。其中一种模型是侧方液压冲击伤（LFPI）啮齿动物模型。LFPI模型可以通过不同的手术程序生成，这些程序可能会影响损伤，并反映在神经行为功能障碍和急性脑电图变化中。在成年雄性Sprague Dawley大鼠的左半球中心，使用手摇钻或电动钻进行颅骨切除术。假手术颅骨切除组通过手摇钻（假手术HMRI）和电动钻（假手术EMRI）进行评估，以通过MRI进行评价。然后，使用液压冲击装置在不同组（TBIH）和（TBIE）中诱导TBI。假损伤大鼠（假手术H/假手术E）接受与TBI大鼠相同的手术程序。在同一手术过程中，将螺钉和微丝电极植入位于新皮层和海马体的大鼠体内，并在TBI后的前7天记录24小时的脑电图活动，以评估急性脑电图癫痫发作和伽马事件耦合（GEC）。与手摇钻相比，电动钻颅骨切除术导致更大的组织损伤和感觉运动缺陷。脑电图分析显示，术后每组至少有一只动物出现急性癫痫发作。电动钻组的TBI和假手术大鼠的癫痫发作总数均显著高于手动颅骨切除的动物（p<0.05）。同样，与假手术H大鼠相比，假手术E大鼠的脑电图功能连接性更低。这些结果表明，与手摇钻相比，电动钻颅骨切除术除了造成LFPI外，还会导致皮质损伤，从而增加创伤后急性癫痫发作的可能性。手术方法的差异可能是损伤变异性的一个原因，这使得临床前TBI研究之间难以复制结果。
