Temporal profiles of axonal injury following impact acceleration traumatic brain injury in rats—a comparative study with diffusion tensor imaging and morphological analysis

Abstract

Traumatic axonal injury (TAI) plays a major role in the development of neurological impairments after traumatic brain injury (TBI), but it is commonly difficult to evaluate it precisely and early with conventional histological biomarkers, especially when the patients experience short-term survival after TBI. Diffusion tensor imaging (DTI) has shown some promise in detecting TAI, but longitudinal studies on the compromised white matter with DTI at early time points (≤72 h) following impact acceleration TBI are still absent. In the present study, rats were subjected to the Marmarou model and imaged with DTI at 3, 12, 24, and 72 h (n = 5 each) post-injury. Using a region-of-interest-based approach, the regions of interest including the corpus callosum, bilateral external capsule, internal capsule, and pyramidal tract were studied. Two DTI parameters, fraction anisotropy and axial diffusivity, were significantly reduced from 3 to 72 h in each region after trauma, corresponding to the gradient of axonal damage demonstrated by immunohistochemical staining of β-amyloid precursor protein and neurofilament light chain. Remarkably, DTI changes predicted the approximate time in the acute phase following TBI. These results indicate that the temporal profiles of diffusion parameters in DTI may be able to provide a tool for early diagnosis of TAI following impact acceleration TBI.

Time-related morphometric studies of neurofilaments in brain contusions

“…Li et al observed a statistically significant gradual time-dependent increase in immunoreactivity (average density) of NF-L (up to 72 hours) in certain structures of the rat brain: the corpus callosum, internal and external capsule and pyramidal tracts [15].…”

“…In majority of studies, NF-H and NF-L were researched [3][4][5]7,10,12,15,16,19,20,23,28]. Neurofilaments at the site of the brain contusion disintegrate, their complete disappearance was observed 1 to 2 weeks following trauma [10,20,22,26].…”

Neurofilaments and traumatic brain injury

“…Należy zauważyć, że istnieją również takie prace, w których obserwowano nie spadek, lecz wzrost immunoreaktywności neurofilamentów po urazie [25,26]. Li i wsp.…”

“…Li i wsp. stwierdzili stopniowy, statystycznie istotny wzrost immunoreaktywności (średniej gęsto-ści) neurofilamentów lekkich -NF-L -wraz z upły-wem czasu po urazie (do 72 godzin) w takich strukturach mózgu szczura, jak: ciało modzelowate, torebka wewnętrzna i zewnętrzna czy drogi piramidowe [26].…”

“…It should be noted that there are also studies which, instead of a decrease, have demonstrated a post-traumatic increase in neurofilament immunoreactivity [25,26]. Li et al have found a gradual, statistically significant increase in immunoreactivity (average density) of light neurofilaments (NF-L) along with the lapse of time after the trauma (up to 72 h) in selected structures of rat brains including the corpus callosum, internal and external capsules or pyramidal tracts [26].…”