Search Results (60)

Diffuse axonal injury (DAI) is one of the most severe consequences of traumatic brain injury (TBI), characterized by widespread axonal damage in the cerebral white matter. DAI plays a crucial role in determining clinical outcomes, significantly contributing to long-term disability and mortality in severe cases. Despite advancements in neuroscience and clinical management, the diagnosis and prognosis of DAI remain challenging due to its complex pathophysiology and the difficulty of detecting axonal damage in its early stages. This study critically analyzes the clinical and post-mortem methodologies used to assess DAI, highlighting their strengths and limitations. Traditional histopathological grading systems provide valuable insights into disease progression, yet their correlation with long-term functional outcomes remains controversial. Advanced neuroimaging techniques, such as diffusion-weighted MRI, have improved lesion detection, although their routine clinical application is still limited. Additionally, emerging approaches involving biomarkers and artificial intelligence-based models hold promise for enhancing diagnostic accuracy and prognostic predictions. By synthesizing current knowledge on DAI, this work aims to outline a comprehensive framework for improving diagnosis and outcome assessment. Furthermore, it seeks to foster collaboration among clinicians and researchers, ultimately advancing the understanding of DAI and refining strategies to improve patient care. Full article

Diffuse axonal brain injury (DAI) is a common, debilitating consequence of traumatic brain injury, yet its detection and severity grading remain challenging in clinical and experimental settings. This study evaluated the sensitivity of diffusion tensor imaging (DTI), histology, and neurological severity scoring (NSS) in assessing injury severity in a rat model of isolated DAI. A rotational injury model induced mild, moderate, or severe DAI in male and female rats. Neurological deficits were assessed 48 h after injury via NSS. Magnetic resonance imaging, including DTI metrics, such as fractional anisotropy (FA), relative anisotropy (RA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD), was performed prior to tissue collection. Histological analysis used beta amyloid precursor protein immunohistochemistry. Sensitivity and variability of each method were compared across brain regions and the whole brain. Histology was the most sensitive method, requiring very small groups to detect differences. Anisotropy-based MRI metrics, especially whole-brain FA and RA, showed strong correlations with histology and NSS and demonstrated high sensitivity with low variability. NSS identified injury but required larger group sizes. Diffusivity-based MRI metrics, particularly RD, were less sensitive and more variable. Whole-brain FA and RA were the most sensitive MRI measures of DAI severity and were comparable to histology in moderate and severe groups. These findings support combining NSS and anisotropy-based DTI for non-terminal DAI assessment in preclinical studies. Full article

Background: Radiotherapy for brain tumors can induce cognitive decline, yet most studies examine white matter (WM) damage six months post-treatment, overlooking early microstructural changes. This study investigated whether early WM changes, as measured by diffusion tensor imaging (DTI) histogram and texture features, can predict later cognitive deficits. Methods: Nineteen adults with brain metastases underwent DTI before and immediately after radiotherapy. Ten features—eight histogram-based and two texture-based—were extracted from normal-appearing WM of major DTI indices. Changes (Δ) in these features, if any, were analyzed via multiple linear regression, correlating them with cognitive performance at four months after therapy. Results: Out of 40 features, four exhibited significant post-radiotherapy changes. These were the mean (AD_mean) and skewness (AD_skewness) of axial diffusivity and the kurtosis of mean diffusivity (MD_kurtosis) and radial diffusivity (RD_kurtosis). Regression identified ΔAD_mean (β = −3.303 × 10⁴, p = 0.002) as negatively and ΔAD_skewness (β = 4.642, p = 0.006) and ΔRD_kurtosis (β = −1.505, p = 0.027) as positively associated with semantic fluency. Conclusions: Early WM microstructural disruptions—particularly axonal damage and heterogeneous injury—correlate with declines in semantic fluency. DTI histogram and texture features may be promising as early non-invasive biomarkers for cognitive risk following radiotherapy. Full article

Background: Traumatic brain injury (TBI) remains a significant global health concern with a substantial socioeconomic impact. Although computed tomography (CT) is the primary initial neuroimaging technique, magnetic resonance imaging (MRI) offers a superior detection of subtle brain injuries. However, the ideal timing for MRI in critically ill patients with TBI remains unclear. Methods: This systematic literature review focused on the timing and utility of MRI in moderate and severe TBI in the early treatment phase. A comprehensive search was conducted using PubMed, employing specific search terms related to MRI timing and prognostication in TBI. The mean duration from admission to first MRI was examined in the conducting medical center for reference. Results: Early MRI, within 72 h post-injury, demonstrated a prognostic value compared with later scans. Diffusion tensor imaging (DTI) performed within 48 to 72 h captured critical pathophysiological changes. The presence of bilateral traumatic axonal injury in the brainstem or thalami on MRI served as a significant predictor of outcome in severe TBI. In pediatric TBI, most institutions performed MRI between seventy-two hours and two weeks post-injury, highlighting variability in practices. The mean interval until the first MRI at the conducting center was 16 days. Conclusions: MRI appears to be a valuable tool for prognostication in moderate to severe TBI, offering additional insights beyond those provided by CT. However, the optimal timing and modality for accurate diagnostic and prognostic utility remain uncertain. Current evidence suggests that MRI performed within 72 h after injury in ICU-treated patients with moderate and severe TBI offers valuable prognostic insights compared with delayed MRI, although further research is needed to establish standardized timing protocols and confirm the clinical impact. Full article

Background: Mild traumatic brain injury (mTBI) is a prevalent neurological condition that results in various physical, emotional, and cognitive impairments. The most common are visual impairments, which affect vision’s perceptual, motor, and sensory aspects. Objective: This paper analyzes the pathophysiology of mild traumatic brain injury (mTBI) and its effects on visual and oculomotor functions, focusing on the deficits of the accommodative system and their underlying mechanism. Findings: mTBI frequently causes diffuse axonal injury, resulting in abnormalities of the neurometabolic cascade that impact the brain’s visual regions. Accommodative anomalies, including insufficiency, infacility, and spasm, are markedly more common in mTBI patients than in the general population. These deficiencies present as a notable delay in accommodation response, diminished peak velocity, and compromised dynamic responses, possibly due to sensory and motor disturbances. Conclusions: Accommodation disorder is a significant but under-examined component of visual sequelae related to mTBI. Future research should concentrate on the sensory and motor factors contributing to these deficiencies to enhance diagnostic precision and customize rehabilitative strategies. Full article

Road traffic accidents (RTAs) are a leading cause of morbidity and mortality worldwide, frequently resulting in traumatic brain injuries (TBIs), skull fractures, and spinal injuries. This manuscript examines the forensic aspects of head trauma caused by RTAs, focusing on the role of autopsy and imaging in diagnosing and characterizing injuries. Through a systematic review of the literature, the study highlights the mechanisms of injury, including high-speed collisions, whiplash, and pedestrian impacts, and explores their pathological consequences, such as subarachnoid hemorrhage, intracranial hemorrhage, and diffuse axonal injury. The differentiation between traumatic and non-traumatic conditions, such as aneurysmal subarachnoid hemorrhage, is emphasized to ensure accurate clinical and forensic assessments. Advances in imaging technologies, particularly virtopsy, are discussed for their potential in non-invasive documentation and analysis of head injuries, while limitations of this approach are acknowledged. Furthermore, the manuscript underscores the importance of preventive measures, including helmet and seatbelt use, vehicle safety innovations, and improved road design, in reducing the incidence and severity of RTAs. By integrating clinical, forensic, and preventive perspectives, this study provides a comprehensive framework for understanding and addressing the burden of head trauma related to RTAs. Full article

Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor deficits. Current therapeutic options for neuronal regeneration post-TBI are limited, although neurotrophins, especially nerve growth factor (NGF), show promise in enhancing recovery. NGF can mitigate excitotoxicity and promote neuroprotection, particularly by intranasal administration, which is attractive because of its non-invasive nature. Case Presentation: A three-year-old boy suffered from severe TBI due to a car accident, leading to multiple complications, including a basilar skull fracture and cerebral venous sinus thrombosis. Initial assessments revealed significant neurological impairments. After intensive care and rehabilitation, the child exhibited gradual improvements in consciousness and motor functions but continued to face challenges, particularly with left-sided hemiparesis. Nine months post-injury, he began intranasal administration of human-recombinant NGF (hr-NGF) as part of a clinical trial. Discussion: Following hr-NGF treatment, the child demonstrated notable advancements in motor function, achieving independent standing and walking. Cognitive assessments indicated improvements in various domains, including verbal comprehension and executive functioning. EEG results showed reduced epileptiform activity. These findings suggest that hr-NGF may facilitate recovery in pediatric TBI cases by enhancing both motor and cognitive outcomes. Conclusions: This case highlights the potential role of intranasal hr-NGF administration as a therapeutic strategy for improving neurological recovery in children with severe TBI. The positive clinical outcomes support further exploration of NGF as a viable treatment option to mitigate long-term sequelae associated with pediatric brain injuries. Full article

Background: Diffusion tensor imaging (DTI), a variant of Diffusion Weighted Imaging (DWI), enables a neuroanatomical microscopic-like examination of the brain, which can detect brain damage using physical parameters. DTI’s application to traumatic brain injury (TBI) has the potential to reveal radiological features that can assist in predicting the clinical outcomes of these patients. What is the ongoing role of DTI in detecting brain alterations and predicting neurological outcomes in patients with moderate to severe traumatic brain injury and/or diffuse axonal injury? Methods: A scoping review of the PubMed, Scopus, EMBASE, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The aim was to identify all potentially relevant studies concerning the role of DTI in TBI. From an initial pool of 3527 publications, 26 articles were selected based on relevance. These studies included a total of 729 patients with moderate to severe TBI and/or diffuse axonal injury. DTI parameters were analyzed to determine their relationship with neurological outcomes post-TBI, with assessments of several brain functions and regions. Results: The studies included various DTI parameters, identifying significant relationships between DTI variations and neurological outcomes following TBI. Multiple brain functions and regions were evaluated, demonstrating the capability of DTI to detect brain alterations with higher accuracy, sensitivity, and specificity than MRI alone. Conclusions: DTI is a valuable tool for detecting brain alterations in TBI patients, offering enhanced accuracy, sensitivity, and specificity compared to MRI alone. Recent studies confirm its effectiveness in identifying neurological impairments and predicting outcomes in patients following brain trauma, underscoring its utility in clinical settings for managing TBI. Full article

Background: Perinatal infection is a major risk factor for diffuse white matter injury (dWMI), which remains the most common form of neurological disability among very preterm infants. The disease primarily targets oligodendrocytes (OL) lineage cells in the white matter but also involves injury and/or dysmaturation of neurons of the gray matter. This study aimed to investigate whether neuroinflammation preferentially affects the cellular compositions of the white matter or gray matter. Method: Neuroinflammation was initiated by intracerebral administration of lipopolysaccharide (LPS) to rat pups at postnatal (P) day 5, and neurobiological and behavioral outcomes were assessed between P6 and P21. Results: LPS challenge rapidly activates microglia and astrocytes, which is associated with the inhibition of OL and neuron differentiation leading to myelination deficits. Specifically, neuroinflammation reduces the immature OLs but not progenitors and causes acute axonal injury (β-amyloid precursor protein immunopositivity) and impaired dendritic maturation (reduced MAP2+ neural fiber density) in the cortical area at P7. Neuroinflammation also reduces the expression of doublecortin in the hippocampus, suggesting compromise in neurogenesis. Utilizing a battery of behavioral assessments, we found that LPS-exposed animals exhibited deficits in sensorimotor, neuromuscular, and cognitive domains. Conclusion: Our overall results indicate that neuroinflammation alone in the early postnatal period can produce cardinal neuropathological features of dWMI. Full article

Quantitative MRI techniques could be helpful to noninvasively and longitudinally monitor dynamic changes in spinal cord white matter following injury, but imaging and postprocessing techniques in small animals remain lacking. Unilateral C5 hemisection lesions were created in a rat model, and ultrashort echo time magnetization transfer (UTE-MT) and diffusion-weighted sequences were used for imaging following injury. Magnetization transfer ratio (MTR) measurements and preferential diffusion along the longitudinal axis of the spinal cord were calculated as fractional anisotropy or an apparent diffusion coefficient ratio over transverse directions. The area of myelinated white matter was obtained by thresholding the spinal cord using mean MTR or diffusion ratio values from the contralesional side of the spinal cord. A decrease in white matter areas was observed on the ipsilesional side caudal to the lesions, which is consistent with known myelin and axonal changes following spinal cord injury. The myelinated white matter area obtained through the UTE-MT technique and the white matter area obtained through diffusion imaging techniques showed better performance to distinguish evolution after injury (AUCs > 0.94, p < 0.001) than the mean MTR (AUC = 0.74, p = 0.01) or ADC ratio (AUC = 0.68, p = 0.05) values themselves. Immunostaining for myelin basic protein (MBP) and neurofilament protein NF200 (NF200) showed atrophy and axonal degeneration, confirming the MRI results. These compositional and microstructural MRI techniques may be used to detect demyelination or remyelination in the spinal cord after spinal cord injury. Full article

This study aimed to clarify the differences between the previously reported mechanisms of sports-related concussion (SRC) injuries without a loss of consciousness in contact and collision sports and the mechanisms of SRC injuries in our cases. Based on two videos of SRC injuries occurring during a men’s rhythmic gymnastics competition (three people were injured), the risk of SRC occurrence was estimated from various parameters using a multibody analysis and eight brain injury evaluation criteria. In the present study, the three SRC impacts that occurred in men’s rhythmic gymnastics showed significant characteristics in duration compared to previously reported cases in the contact sports. This suggests that the occurrence of SRC may have been caused by a different type of impact from that which causes SRC in contact sports (e.g., tackling). In addition, calculation of the strain indicating the rate of brain deformation suggested a risk of nerve swelling in all cases involving type 2 axonal injuries. Therefore, when reexamining sports-related head injuries, it is important to recognize the characteristics and mechanisms of SRC that occur in each different sport, as well as the symptoms and course of SRC after injury. Full article

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, we explore these pathogenic mechanisms utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice. We observed a significant elevation of Na⁺/H⁺ exchanger protein (NHE1) expression in GFAP⁺ reactive astrocytes, IBA1⁺ microglia, and OLIG2⁺ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus) after r-mTBI. This elevation was accompanied by astrogliosis, microgliosis, and the accumulation of amyloid precursor protein (APP). Mice subjected to r-mTBI displayed impaired motor learning and spatial memory. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as pathological signatures of gliosis, oxidative stress, axonal damage, and white matter damage. These findings indicate NHE1 upregulation plays a role in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 may be a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function. Full article

Diffuse axonal injury (DAI) following sudden acceleration and deceleration can lead to cognitive function decline. Various treatments have been proposed. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique, is a potential treatment for enhancing neuroplasticity in cases of brain injury. The therapeutic efficacy of rTMS on cognitive function remains unconfirmed. This study investigated the effects of rTMS and the underlying molecular biomechanisms using a rat model of DAI. Sprague–Dawley rats (n = 18) were randomly divided into two groups: one receiving rTMS after DAI and the other without brain stimulation. All rats were subjected to sudden acceleration and deceleration using a DAI modeling machine to induce damage. MRI was performed to confirm the DAI lesion. The experimental group received rTMS at a frequency of 1 Hz over the frontal cortex for 10 min daily for five days. To assess spatial memory, we conducted the Morris water maze (MWM) test one day post-brain damage and one day after the five-day intervention. A video tracking system recorded the escape latency. After post-MWM tests, all rats were euthanized, and their brain tissues, particularly from the hippocampus, were collected for immunohistochemistry and western blot analyses. The escape latency showed no difference on the MWM test after DAI, but a significant difference was observed after rTMS between the two groups. Immunohistochemistry and western blot analyses indicated increased expression of BDNF, VEGF, and MAP2 in the hippocampal brain tissue of the DAI-T group. In conclusion, rTMS improved cognitive function in the DAI rat model. The increased expression of BDNF, VEGF, and MAP2 in the DAI-T group supports the potential use of rTMS in treating cognitive impairments associated with DAI. Full article

Traumatic brain injury (TBI) significantly contributes to death and disability worldwide. However, treatment options remain limited. Here, we focus on a specific pathology of TBI, diffuse axonal brain injury (DABI), which describes the process of the tearing of nerve fibers in the brain after blunt injury. Most protocols to study DABI do not incorporate a specific model for that type of pathology, limiting their ability to identify mechanisms and comorbidities of DABI. In this study, we developed a magnetic resonance imaging (MRI) protocol for DABI in a rat model using a 3-T clinical scanner. We compared the neuroimaging outcomes with histologic and neurologic assessments. In a sample size of 10 rats in the sham group and 10 rats in the DABI group, we established neurological severity scores before the intervention and at 48 h following DABI induction. After the neurological evaluation after DABI, all rats underwent MRI scans and were subsequently euthanized for histological evaluation. As expected, the neurological assessment showed a high sensitivity for DABI lesions indicated using the β-APP marker. Surprisingly, however, we found that the MRI method had greater sensitivity in assessing DABI lesions compared to histological methods. Out of the five MRI parameters with pathological changes in the DABI model, we found significant changes compared to sham rats in three parameters, and, as shown using comparative tests with other models, MRI was the most sensitive parameter, being even more sensitive than histology. We anticipate that this DABI protocol will have a significant impact on future TBI and DABI studies, advancing research on treatments specifically targeted towards improving patient quality of life and long-term outcomes. Full article

Secondary neurodegeneration refers to the final result of several simultaneous and sequential mechanisms leading to the loss of substance and function in brain regions connected to the site of a primary injury. Stroke is one of the most frequent primary injuries. Among the subtypes of post-stroke secondary neurodegeneration, axonal degeneration of the corticospinal tract, also known as Wallerian degeneration, is the most known, and it directly impacts motor functions, which is crucial for the motor outcome. The timing of its appearance in imaging studies is usually considered late (over 4 weeks), but some diffusion-based magnetic resonance imaging (MRI) techniques, as diffusion tensor imaging (DTI), might show alterations as early as within 7 days from the stroke. The different sequential pathological stages of secondary neurodegeneration provide an interpretation of the signal changes seen by MRI in accordance with the underlying mechanisms of axonal necrosis and repair. Depending on the employed MRI technique and on the timing of imaging, different rates and thresholds of Wallerian degeneration have been provided in the literature. In fact, three main pathological stages of Wallerian degeneration are recognizable—acute, subacute and chronic—and MRI might show different changes: respectively, hyperintensity on T2-weighted sequences with corresponding diffusion restriction (14–20 days after the injury), followed by transient hypointensity of the tract on T2-weighted sequences, and by hyperintensity and atrophy of the tract on T2-weighted sequences. This is the main reason why this review is focused on MRI signal changes underlying Wallerian degeneration. The identification of secondary neurodegeneration, and in particular Wallerian degeneration, has been proposed as a prognostic indicator for motor outcome after stroke. In this review, the main mechanisms and neuroimaging features of Wallerian degeneration in adults are addressed, focusing on the time and mechanisms of tissue damage underlying the signal changes in MRI. Full article