Title: Injury characteristics of the Papez circuit in patients with diffuse axonal injury: a diffusion tensor tractography study.

We investigate the characteristics of injury of four portions of the Papez circuit in patients with diffuse axonal injury (DAI), using diffusion tensor tractography (DTT). Thirty-four consecutive patients with DAI and 30 normal control subjects were recruited. Four portions of the Papez circuit were reconstructed: the fornix, cingulum, thalamocingulate tract, and mammillothalamic tract. Analysis of DTT parameters [fractional anisotropy (FA) and tract volume (TV)] and configuration (narrowing, discontinuation, or non-reconstruction) was performed for each portion of the Papez circuit. The Memory Assessment Scale (MAS) was used for the estimation of cognitive function. In the group analysis, decreased fractional anisotropy and tract volume of the entire Papez circuit were observed in the patient group compared with the control group (p < 0.05). In the individual analysis, all four portions of the Papez circuit were injured in terms of DTT parameters or configuration. Positive correlation was observed between TV of the fornix and short-term memory on MAS r = 0.618, p < 0.05), and between FA of the fornix and total memory on MAS (r = 0.613, p < 0.05). We found that all four portions of the Papez circuit in the patient group were vulnerable to DAI, and among four portions of the Papez circuit, the fornix was the most vulnerable portion in terms of injury incidence and severity.

Scooping Rice Into a Glass and Putting a Cell Phone in the Refrigerator: Action Slips in an Individual With a Diffuse Axonal Injury.

A 39-year-old man with a diffuse axonal injury self-presented to the cognitive function clinic of the Ashikaga Red Cross Hospital complaining of behavioral errors in his daily life, such as scooping hot rice into a glass instead of a bowl or forgetting to turn off the gas stove after cooking. This type of error has been referred to as an action slip-a form of unintentional behavioral error that occurs when an individual attempts to perform an automatic and/or familiar task. In this case, action slips occurred nine times a day on average and had a serious and long-term impact on the man's daily quality of life. To reduce the impact of action slips, we created a one-on-one cognitive intervention that used a combination of mnemonic strategies, such as verbalizing his actions as he carried them out, and external aids, including a waist pouch, a voice-controlled artificial intelligence (AI) speaker, and an AI key finder. After 3 years of intervention, the man reported some improvement in his daily activities and a reduction in the number of action slips. Thus, intervention strategies for individuals with a diffuse axonal injury may benefit from targeting action slips. To our knowledge, this is the first detailed description of action slips in an individual with a diffuse axonal injury.

The Behavioral Neuroscience of Traumatic Brain Injury.

Traumatic brain injury is a calamity of various causes, pathologies, and extremely varied and often complex clinical presentations. Because of its predilection for brain systems underlying cognitive and complex behavioral operations, it may cause chronic and severe psychiatric illness that requires expert management. This is more so for the modern epidemic of athletic and military brain injuries which are dominated by psychiatric symptoms. Past medical, including psychiatric, history, and comorbidities are important and relevant for formulation and management. Traumatic brain injury is a model for other neuropsychiatric disorders and may serve as an incubator of new ideas for neurodegenerative disease.

Effect of α7nAChR on learning and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

Repetitive TMS does not improve cognition in patients with TBI: A randomized double-blind trial.

OBJECTIVE: To determine whether high-frequency repetitive transcranial magnetic stimulation (rTMS) improves cognition in patients with severe traumatic brain injury. METHODS: A single-center, randomized, double-blind, placebo-controlled study of rTMS was conducted in patients aged 18-60 years with chronic (>12 months postinjury) diffuse axonal injury (DAI). Patients were randomized to either a sham or real group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Neuropsychological assessments were performed at 3 time points: at baseline, after the 10th rTMS session, and 90 days after intervention. The primary outcome was change in executive function evaluated using the Trail Making Test Part B. RESULTS: Thirty patients with chronic DAI met the study criteria. Between-group comparisons of performance on TMT Part B at baseline and after the 10th rTMS session did not differ between groups (p = 0.680 and p = 0.341, respectively). No significant differences were observed on other neuropsychological tests. No differences in adverse events between treatment groups were observed. CONCLUSIONS: Cognitive function in individuals with chronic DAI is not improved by high-frequency rTMS over the left DLPFC, though it appears safe and well-tolerated in this population. CLINICALTRIALSGOV IDENTIFIER: NCT02167971. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for individuals with chronic DAI, high-frequency rTMS over the left DLPFC does not significantly improve cognition.

Predictive value of early MRI findings on neurocognitive and psychiatric outcomes in patients with severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is the major public health problem worldwide, particularly in the Middle East. Diffuse axonal injury (DAI) is commonly found in TBI. Although DAI can lead to physical and psychosocial disabilities, its prognostic value is still a matter of debate. Magnetic Resonance (MR) is more sensitive for detecting DAI lesions. OBJECTIVE: To identify the radiological and clinical factors associated with the functional capacity one year after the traumatic brain injury. METHODS: The study included 251 patients with severe head trauma for whom Brain MRI was done within one month after injury. Demographic, clinical, and radiological data were collected during hospitalization. Neurocognitive and psychiatric evaluation were done one year thereafter. RESULTS: DAI was more frequent in our patients. Psychiatric disorders, cognitive impairment, and poor functional outcome were more common in patients with DAI especially those with cerebral hemisphere and brain stem lesion, and mixed lesions. Duration of post traumatic amnesia (DPTA), lost consciousness and hospital stay (DHS) as well as the volume of diffuse axonal injury (DAI) were associated with poor neurocognitive outcome. DPTA, and DAIV may be considered independent factors that could predict the neurocognitive outcome. CONCLUSION: MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with poor long-term neurocognitive and psychiatric outcomes.

Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial.

BACKGROUND: Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800-900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. METHODS/DESIGN: This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm2, 10 J/cm2) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation. DISCUSSION: This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03281759 . Registered on 13 September 2017.

Facial emotion recognition in patients with focal and diffuse axonal injury.

OBJECTIVE: Facial emotion recognition impairment has been well documented in patients with traumatic brain injury. Studies exploring the neural substrates involved in such deficits have implicated specific grey matter structures (e.g. orbitofrontal regions), as well as diffuse white matter damage. Our study aims to clarify whether different types of injuries (i.e. focal vs. diffuse) will lead to different types of impairments on facial emotion recognition tasks, as no study has directly compared these patients. METHODS: The present study examined performance and response patterns on a facial emotion recognition task in 14 participants with diffuse axonal injury (DAI), 14 with focal injury (FI) and 22 healthy controls. RESULTS: We found that, overall, participants with FI and DAI performed more poorly than controls on the facial emotion recognition task. Further, we observed comparable emotion recognition performance in participants with FI and DAI, despite differences in the nature and distribution of their lesions. However, the rating response pattern between the patient groups was different. CONCLUSION: This is the first study to show that pure DAI, without gross focal lesions, can independently lead to facial emotion recognition deficits and that rating patterns differ depending on the type and location of trauma.

Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study.

OBJECTIVE: Diffuse axonal injury (DAI) is prevalent in traumatic brain injury (TBI), and is often associated with poor outcomes and cognitive impairment, including memory deficits. Few studies have explored visual memory after TBI and its relationship to executive functioning. Executive functioning is crucial for remembering an object's location, operating devices, driving, and route finding. We compared visual memory performance via the Rey-Osterrieth Complex Figure (ROCF) test 6 and 12 months after DAI. METHOD: In total, 40 patients (mean age 28.7 years; 87.5% male) with moderate-to-severe DAI following a road traffic accident completed the 1-year follow-up. There was a three-phase prospective assessment. In phase 1 (1-3 months after trauma), patients completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). In phases 2 (6 months) and 3 (12 months), they completed the BDI, STAI, and a neuropsychological battery [ROCF copy and recall, digit span forward/backward, Grooved Pegboard test, intelligence quotient (IQ) by Wechsler Adult Intelligence Scale-III (WAIS-III)]. RESULTS: There was an improvement in ROCF recall over time (p=0.013), but not ROCF copy (p=0.657).There was no change in executive function (Savage scores) copy (p=0.230) or recall (p=0.155). Age, years of education, severity of the trauma, and IQ did not influence ROCF recall improvement. CONCLUSION: There are time-dependent improvements in visual memory in patients with DAI. Neuroplasticity in the 1st months after trauma provides an opportunity for visuospatial memory learning. The present findings may be useful to formulate management plans for long-term TBI rehabilitation.

Correlations between Cognitive Impairments and Employment Status in Patients with Diffuse Axonal Injury.

Patients with diffuse axonal injury (DAI) may initially present with prominent physical impairments, but their cognitive dysfunctions are more persistent and are attributable to later unemployment. In this study, we analyzed how the findings of early and delayed neuropsychological assessments correlated with employment outcome of patients with DAI. A total of 56 patients with DAI without motor or visual dysfunction were included in this study. The neuropsychological battery consisted of the Wechsler Adult Intelligent Scale - Revised (WAIS-R), Wechsler Memory Scale - Revised (WMS-R), Trail Making Test (TMT), Wisconsin Card Sorting Test (WCST), and Word Fluency Test (WFT). This battery of tests was administered twice in early stage after injury and in later stage. The results of all of the neuropsychological tests improved significantly (P <0.001) between the early and later assessments. All scores other than TMT part A and B improved to the normal range (Z-score ≥ 2). The patient characteristics (age, gender, initial Glasgow Coma Scale, and duration of posttraumatic amnesia) had no relationship to the outcome. The results of TMT part B, however, were significantly correlated with employment outcome in both the early and later assessments (P = 0.01, 0.04). Given that TMT evaluates visual attention, we surmise that a lack of attention may be the core symptom of the cognitive deficit and cause the re-employment failure in patients with DAI. TMT part B in both early and later assessments has the potential to accurately predict chronic functional outcome.

Repetitive Transcranial Magnetic Stimulation (rTMS) for the cognitive rehabilitation of traumatic brain injury (TBI) victims: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) has been proposed as a new tool in neurological rehabilitation of victims of traumatic brain injury (TBI). However, its usefulness to treat this condition has never been tested rigorously. The primary goal is to conduct a study protocol to determine whether rTMS used to cognitive rehabilitation of victims of TBI with diffuse axonal injury (DAI) is a safe instrument and if it enhances cognitive function recovery. METHODS: Double-blind randomized controlled trial of patients with diffuse axonal injury. Thirty-six patients will be randomized to either an active coil group or sham group in a 1:1 ratio. rTMS protocol: 10 sessions of high-frequency rTMS (10 Hz) over the left dorsolateral prefrontal cortex (DLPFC). Cortical Excitability measures will be obtained. Neuropsychological evaluations will be performed 1 week before, 1 week and 3 months after rTMS. There are 2 study hypotheses: (1) rTMS over the left DLPFC in patients with DAI will improve cognitive function and (2) whether rTMS is safe in TBI patients. DISCUSSION: This study evaluates the immediate and delayed effects of rTMS over the DLPFC on the cognitive domain of patients with DAI following TBI. rTMS has shown good results in treating major depression and may be promising for patients with TBI. As such, the results of this study can greatly modify the cognitive rehabilitation strategies. TRIAL REGISTRATION: This trial was registered in clinicaltrials.gov ( NCT02167971 ) on 17 June 2014.

Traumatic axonal injury and persistent emotional lability in an adolescent following moderate traumatic brain injury: A case study.

A 15-year-old male was treated secondary to sustaining a moderate traumatic brain injury (moderate TBI). Symptom self-report, and computerized and paper-and-pencil-based neurocognitive, vestibular/ocular motor, and imaging data were used throughout to document impairment and recovery. The patient demonstrated persistent emotional lability concurrent with vestibular impairment. In addition to clinical evaluation and management, the patient also underwent susceptibility-weighted imaging, which revealed axonal shearing across the corpus callosum and areas innervating the prefrontal cortex. Paper-and-pencil neurocognitive measures revealed persisting deficits, despite normal-appearing computerized test results. Implications of this case underline the importance of an integrative evaluation process including clinical interview, neurocognitive and vestibular/ocular physical therapy, and advanced neuroimaging, especially in cases with atypical presentation.

Fatigue, psychosocial adaptation and quality of life one year after traumatic brain injury and suspected traumatic axonal injury; evaluations of patients and relatives: a pilot study.

OBJECTIVE: To describe fatigue and its relationship to cognition, psychosocial adjustment, quality of life (QoL), work status and relative's experiences 12 months after suspected traumatic axonal injury (TAI). METHODS: Eighteen patients were assessed with the Daily Fatigue Impact Scale (D-FIS), the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), the European Questionnaire 5 Dimensions health-related quality of life, the Glasgow Coma Outcome Scale Extended, and the European Brain Injury Questionnaire (EBIQ) (patient and relative). Return to work was registered. RESULTS: At 1 year, fatigue still caused great problems in daily life. Although fatigue and cognition (BNIS) did not correlate, the more fatigued patients subjectively experienced significantly more cognitive dysfunction. Although D-FIS and QoL did not correlate, most patients reported that feelings of tiredness and dullness related to having lower QoL. However, lower QoL was associated with cognitive and attention disability (BNIS), subjective perception of executive dysfunction, lack of motivation, and mood disturbances (EBIQ). Neither fatigue nor cognition associated with return to work. The general consequences of TAI showed good agreement between patients' and relatives' experiences. CONCLUSION: The patient's subjective experience of the impact of TAI seems to be most essential, as it is the objective reality that the patient responds to, and this should therefore be assessed and treated.

Characterising effects of impact velocity on brain and behaviour in a model of diffuse traumatic axonal injury.

The velocity of impact between an object and the human head is a critical factor influencing brain injury outcomes but has not been explored in any detail in animal models. Here we provide a comprehensive overview of the interplay between impact velocity and injury severity in a well-established weight-drop impact acceleration (WDIA) model of diffuse brain injury in rodents. We modified the standard WDIA model to produce impact velocities of 5.4, 5.85 and 6.15 m/s while keeping constant the weight and the drop height. Gradations in impact velocity produced progressive degrees of injury severity measured behaviourally, electrophysiologically and anatomically, with the former two methods showing greater sensitivity to changes in impact velocity. There were impact velocity-dependent reductions in sensorimotor performance and in cortical depth-related depression of sensory cortex responses; however axonal injury (demonstrated by immunohistochemistry for ß-amyloid precursor protein and neurofilament heavy-chain) was discernible only at the highest impact velocity. We conclude that the WDIA model is capable of producing graded axonal injury in a repeatable manner, and as such will prove useful in the study of the biomechanics, pathophysiology and potential treatment of diffuse axonal injury.

Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes.

BACKGROUND: Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the central fluid percussion injury (cFPI) TAI model in mice, the neuroinflammatory and astroglial response and behavioral changes are unknown. METHODS: Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data). RESULTS: At all post-injury time points, ß-amyloid precursor protein (ß-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood-brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P<0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls. CONCLUSIONS: Traumatic axonal injury TAI resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting TAI.

Cognitive impact of traumatic axonal injury (TAI) and return to work.

OBJECTIVE: Axonal injury (AI) after traumatic brain injury (TBI) is often overlooked as an explanation for cognitive complaints when no damage is detected by computed tomography. The purpose was to assess cognition during the 12 months following a TBI and suspected traumatic axonal injury (TAI). METHODS: The sample included 17 patients younger than 65 years old, however one died. In the acute phase and at 6 and 12 months, cognition, reaction time, psychomotor performance and finger tapping speed were assessed. Working memory and work status were added at 12 months. Acute MRI findings were recorded. RESULTS: After 1 year, all patients still showed cognitive dysfunction. A recovery had been noted at 6 months, but a cognitive decline was indicated for the majority at 12 months. The sick-listed patients had TAI located in the corpus callosum and the brainstem. They were cognitively more impaired and in more areas than the four patients who had returned to work. CONCLUSION: Cognitive screening can identify the long-term impact of TAI identified by conventional MRI, used as a routine clinical technique. For rehabilitation and for insurance-related matters, these injuries must be taken seriously, as a deterioration over time might occur. Further research is needed.

Exploring temporospatial changes in glucose metabolic disorder, learning, and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and contributes significantly to cognitive deficits. The mechanisms underlying these cognitive deficits are often associated with complex metabolic alterations. However, the relationships between temporospatial alterations in cerebral glucose metabolism and the pathophysiology of DAI-related learning and memory dysfunction are not yet completely understood. We used a small animal positron emission tomography (PET) scanner with 2-[F-18]-fluoro-2-deoxy-D-glucose (¹8F-FDG) as a molecular probe to evaluate temporospatial glucose metabolism in vulnerable areas of rats with DAI. The Morris water maze (MWM) was used to evaluate the development and progression of learning and memory dysfunction. Compared to the sham-treated group, PET-MRI fusion images showed that glucose metabolism was reduced in animals with DAI. In addition, the standardized uptake value (SUV) of ¹8F-FDG was significantly decreased in the sensorimotor cortex, hippocampus, corpus callosum, caudate putamen, brain stem, and cerebellum at days 1, 3, and 7 after injury. SUV returned to baseline levels by 30 days after injury. The escape latency of the injured group was significantly increased, and the percentages of distance travelled and time spent in the target quadrant were significantly decreased 1 month after injury. These effects persisted for 3 months. SUVs in the hippocampus at the acute stage were significantly correlated with MWM performance during the recovery stage of DAI. These results demonstrate that microstructural injury-induced hypometabolism in the hippocampus at the acute stage are all significantly correlated with learning and memory dysfunctions during the recovery stage of DAI.

Independence in managing one's finances after traumatic brain injury.

PRIMARY OBJECTIVE: To establish whether the budgeting task of the Instrumental Activities of Daily Living (IADL) Profile discriminates individuals with a traumatic brain injury (TBI) from healthy controls and to identify the nature of the observed difficulties. METHOD: This study tested 27 adults with moderate or severe TBI and 27 controls matched for age, sex and education on the budgeting task of the IADL Profile. The budgeting task is a complex real-world problem involving the preparation of a yearly budget for an individual living on a fixed income with the goal of saving money to purchase a car. MAIN RESULTS: The results showed that TBI subjects, the majority of whom had documented frontal lesions and/or diffuse axonal injury based on CT scan reports, were more likely than control subjects to experience difficulties on all task-related operations (planning, carrying out and verifying attainment of goal), with planning being particularly affected. These deficits were shown to impact on financial abilities, an issue of particular concern for TBI individuals reporting full responsibility of their finances. CONCLUSIONS: The budgeting task of the IADL Profile discriminates TBI subjects from controls. Planning was shown to be the most significant difficulty underlying reduced independence in the task.

[Care continuity for pediatric patients with higher cortical dysfunction after traumatic brain injury].

Higher cortical dysfunction after traumatic brain injury(TBI) is one of the most important aspects for rehabilitation. Main etiology is traffic accidents and classification after TBI is diffuse axonal injury, cerebral contusion, etc. Though Wechsler Intelligence Scale for Children-III, Kaufman assessment battery for children, Trail Making Test, etc. are used for assessing higher cortical dysfunction in children, the most important evaluation method is to get information precisely from his/her families and teachers. Memory disturbance, attention deficit and dyscontrol of feeling are the top 3 symptoms of higher cortical dysfunction in children with TBI. Support for re-entrance to schools should be begun as fast as possible with cooperation among hospitals, schools and homes. As many problems are observed in the aspects of study, behavior, communication, etc, a lot of support from the professional staffs is necessary. After the school age, support should be continued by stuffs for adult cases.

[Effect of Chinese medicine Huishen granule on cognitive outcome following diffuse axonal injury: experiment with rats].

OBJECTIVE: To investigate the influence of Chinese medicine Huishen granule (HG) containing ginseng, grassleaved sweet flag rhizome, pilose deer antler, etc, on learning and memory functions in diffuse axonal injury (DAI) and the mechanisms thereof. METHODS: Impact acceleration method was used to establish DAI Wistar rat models. Twenty model rats were randomly divided into 2 equal groups, the DAI+HG group treated with gastric perfusion of HG 3 times a day since 24 h after the establishment of model for 14 days, and the DAI group without treatment. Ten rats underwent sham operation as controls. Fourteen days after the injury, Morris water maze (MWM) test was used to detect the rat's abilities of learning and memory for continuous 5 days. The changes of escape latency in acquisition of the task, the percentage of time spent in target quadrant, and the number of crossing the point of original platform in probe test were recorded. At day 20 after the-operation, the rats were subjected to long-term potentiation (LTP) recording in hippocampus to measure the percentage of slope and baseline of excitatory post-synaptic potential (EPSP). Two rats from each group were killed 24 h, 14 d, and 20 d after the operation with their brains taken out, HE and immunohistochemical staining were employed to exam the brain lesion at 24 h, day 14 and 20 post-injury. RESULTS: The escape latency of the DAI group was (32.8+/-4.6) s, significantly longer than those of the DAI+HG and sham operation groups [(20.3+/-0.7) and (16.8+/-0.8) s respectively, both P<0.05]. The target quadrant staying time percentage and number of platform location crossings of the DAI group were (36.4+/-3.2)% and 4.5+/-0.6 respectively, both significantly less than those of the DAI+HG and sham operation groups [(46.0+/-2.4)% and 6.8+/-0.8, and (46.9+/-2.1)% and 8.1+/-0.8 respectively, all P<0.05]. The LTP level of the DAI group was (101.4+/-3.3)%, significantly lower than those of the DAI+HG and sham operation groups [(116.3+/-6.7)% and (117.9+/-2.8)% respectively, both P<0.05]. No significant differences in the parameters were found between the DAI+HG and sham operation groups (all P>0.05). Classical pathological changes of DAI occurred in the brains of the DAI and DAI+HG groups at the time point of 24 h, and mitigated partly at the time points of day 14 and 20. CONCLUSION: The learning and memory impairment of DAI was ameliorated significantly with the treatment of Chinese medicine HG, owing to the recuperation of synaptic plasticity in hippocampal area.