- 學位論文
以β－澱粉樣前驅蛋白作為貓創傷性軸突損傷生物標記之評估
A Study on Beta Amyloid Precursor Protein as a Biomarker for Traumatic Axonal Injury in Cats
摘要
創傷性腦傷(Traumatic brain injury)是獸醫法醫案件中最常見的死因之一，而創傷性軸突損傷(Traumatic axonal injury)幾乎普遍繼發於創傷性腦傷。β-澱粉樣蛋白前驅蛋白(βamyloid precursor protein)的免疫化學染色和陽性訊號型態的判讀在人類法醫學中是診斷早期軸突損傷的準則。在動物中，關於βAPP的文獻僅有數篇，而幾乎沒有關於犬貓的相關研究。因此，本研究旨在透過βAPP診斷動物的創傷性腦傷，並嘗試釐清TAI中組織病理及免疫化學染色與腦傷嚴重程度的關聯。在此研究中，樣本來源為常規法醫解剖中收集的貓大體。其中被診斷有創傷性腦傷的個體會被依照傷害程度分成兩組，而沒有發現創傷性腦傷的個體則分到控制組。樣本會收集每個個體的整顆腦，經妥善固定後依標準化的方式切片後選取代表性的區域進行判讀。腦組織會經過組織病理檢查、βAPP陽性訊號（軸突球）會經計數並和腦傷的嚴重程度做統計上的對照。此研究中共採樣39隻有創傷性腦傷的貓和20隻無腦傷的貓。結果顯示，診斷創傷性腦傷的病例中，64.1%有軸突損傷的陽性訊號，軸突球計數的總合(Axonal bulb count)在嚴重腦傷中，相較於較輕微腦傷會顯著地增加，且在胼胝體、大腦白質及海馬迴中區域性軸突球計數的總合亦存在著嚴重腦傷較輕度腦傷中顯著增加的趨勢。統計的數值中，腦傷過後產生陽性軸突球訊號的最短時間介於0.5至2小時間。貓隻中，最常表現創傷性軸突損傷的區域為大腦白質，而後是小腦白質及腦幹，代表著大腦白質對於偵測創傷性軸突損傷很敏感。此外，軸突球計數可能在對撞傷的情況下具有額外診斷價值。總結來說，此研究可謂伴侶動物創傷性軸突損傷中一具有前瞻性的研究。
並列摘要
Traumatic brain injury (TBI) is one of the most common causes of death in veterinary forensic cases, and traumatic axonal injury (TAI) is almost a universal consequence of TBI. The pattern analysis for immunohistochemistry (IHC) against beta-amyloid precursor protein (βAPP) is a gold standard for early detecting axonal injuries in human forensic neuropathology. In animals, only several studies on TAI have been performed, but there is scanty research on TAI of dogs or cats. The study aims to detect TAI in animals with TBI by βAPP IHC and try to correlate the severity of head injury to histopathological and immunohistochemical results of TAI. Fifty-nine cat carcasses were collected from routinely forensic necropsy cases. Cats with TBI were separately grouped into two groups according to the severity of the head injury, while cats without TBI were selected for the control group. The entire brains of animals with TBI were collected and underwent appropriate fixation, and representative sections were selected following standardized serial sections. The histopathological examination and quantification of positive signals of βAPP IHC, the axonal retraction bulbs, in cats with TBI were calculated and correlated to the severity of the head injury. Thirty-nine cats with TBI and twenty cats without TBI are collected in this study. The results revealed that 64.1% of TBI cases demonstrated positive signals of axonal injuries. The total axonal bulb count (ABC) is remarkably increased in severer head injuries compared to milder head injuries, and the regional ABC is also significantly higher in more severe TBI in corpus callosum, cerebral white matter and hippocampus. The shortest post-traumatic interval of the presence of axonal bulbs is between 0.5-2hr. The most frequent location to perform TAI in cats was cerebral white matter and following cerebellar white matter and medulla oblongata, indicating that cerebral white matter may be a sensitive region to detect TAI. Furthermore, the axonal bulb count may have a diagnostic value for determining the coup and contrecoup lesions. In conclusion, the research may shed light on the early detection of TAI in companion animals.
參考文獻
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