Donat Cornelius K, Walter Bernd, Kayser Tanja, Deuther-Conrad Winnie, Schliebs Reinhard, Nieber Karen, Bauer Reinhard, Härtig Wolfgang, Brust Peter
Institute of Interdisciplinary Isotope Research, Leipzig, Germany.
Int J Dev Neurosci. 2010 Feb;28(1):31-8. doi: 10.1016/j.ijdevneu.2009.10.001. Epub 2009 Oct 12.
Traumatic brain injury is a leading cause of death and disability in children. Studies using adult animal models showed alterations of the central cholinergic neurotransmission as a result of trauma. However, there is a lack of knowledge about consequences of brain trauma on cholinergic function in the immature brain. It is hypothesized that trauma affects the relative acetylcholine esterase activity and causes a loss of cholinergic neurons in the immature brain. Severe fluid percussion trauma (FP-TBI, 3.8+/-0.3atm) was induced in 15 female newborn piglets, monitored for 6h and compared with 12 control animals. The hemispheres ipsilateral to FP-TBI obtained from seven piglets were used for acetylcholine esterase histochemistry on frozen sagittal slices, while regional cerebral blood flow and oxygen availability was determined in the remaining eight FP-TBI animals. Post-fixed slices were immunohistochemically labelled for choline acetyltransferase as well as for low-affinity neurotrophin receptor in order to characterize cholinergic neurons in the basal forebrain. Regional cerebral blood flow and brain oxygen availability were reduced during the first 2h after FP-TBI (P<0.05). In addition, acetylcholine esterase activity was significantly increased in the neocortex, basal forebrain, hypothalamus and medulla after trauma (P<0.05), whereas the number of choline acetyltransferase and low-affinity neurotrophin receptor positive cells in the basal forebrain were unaffected by the injury. Thus, traumatic brain injury evoked an increased relative activity of the acetylcholine esterase in the immature brain early after injury, without loss of cholinergic neurons in the basal forebrain. These changes may contribute to developmental impairments after immature traumatic brain injury.
创伤性脑损伤是儿童死亡和残疾的主要原因。使用成年动物模型的研究表明，创伤会导致中枢胆碱能神经传递发生改变。然而，对于未成熟脑内脑损伤对胆碱能功能的影响，我们还知之甚少。据推测，创伤会影响未成熟脑中乙酰胆碱酯酶的相对活性，并导致胆碱能神经元的丧失。对15只新生雌性仔猪施加严重液体冲击伤（FP-TBI，3.8±0.3大气压），监测6小时，并与12只对照动物进行比较。从7只仔猪获取的与FP-TBI同侧的大脑半球用于冰冻矢状切片的乙酰胆碱酯酶组织化学检测，而其余8只FP-TBI动物则测定局部脑血流量和氧供应情况。对后固定切片进行免疫组织化学标记，以检测胆碱乙酰转移酶以及低亲和力神经营养因子受体，从而对基底前脑的胆碱能神经元进行表征。FP-TBI后的最初2小时内，局部脑血流量和脑氧供应减少（P<0.05）。此外，创伤后新皮层、基底前脑、下丘脑和延髓中的乙酰胆碱酯酶活性显著增加（P<0.05），而基底前脑中胆碱乙酰转移酶和低亲和力神经营养因子受体阳性细胞的数量不受损伤影响。因此，创伤性脑损伤在损伤后早期会引起未成熟脑中乙酰胆碱酯酶的相对活性增加，而基底前脑中的胆碱能神经元并未丧失。这些变化可能导致未成熟创伤性脑损伤后的发育障碍。
