OBJECTIVETo introduce a new animal model of graded mechanical primary brainstem injury (BSI).

METHODSAltogether 45 rabbits were subjected to BSI by type II biological impact machine designed by the Third Military Medical University. The animals were divided into 4 experimental groups (n equal to 10) and 1 control group (n equal to 5) according to different magnitudes of impact pressure imposed on the occipital nodule: Group 1, 500-520 kPa; Group 2, 520-540 kPa; Group 3, 540-560 kPa; Group 4, 560-580 kPa and Group 5, 0 kPa with 20 kPa increase in each grade. The impact depth was a constant 0.5 cm. After injury, the clinical symptoms and signs as well as pathological changes were observed.

RESULTSRabbits in Group 1 revealed mild physiological reaction of BSI. They had localized cerebral contusion with punctate hemorrhage and subarachnoid hemorrhage (SAH) was limited to the peripheral tissues at the impact area. In Group 2, obvious physiological reaction was observed. Local pathological lesions reached the superficial layer of brainstem tissues; focal hemorrhage and girdle-shaped SAH in basilar pon were observed under microscope. In Group 3, BSI was more severe with a long respiratory depression. Pathological lesions reached the inner portion of brainstem with massive hemorrhage and the whole brainstem was wrapped by subarachnoid hematoma. In Group 4, most rabbits died due to severe BSI. Pathological lesions deepened to the central brainstem with wide pathological change, rapture of the medulla oblongata central canal. Group 5 was the control group, with normal brainstem structure and no lesion observed.

CONCLUSIONThis model successfully simulates different levels of brainstem mechanical injury and clearly shows the subsequent pathological changes following injury. It takes two external parameters (impact pressure and depth) and has a similar injury mechanism to clinical accelerating BSI. Moreover it is reproducible and stable, thus being be- neficial for exploring pathophysiological mechanism, diagnosis and forensic identification of various degrees of BSI.

Multipotent neural stem cells (NSCs) are operationally defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating CNS regions. Thus their use as a graft material can be considered analogous to hematopoietic stem cell-mediated reconstitution and gene transfer. The recognition that NSCs propagated in culture could be reimplanted into mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that heretofore has been refractory to intervention. We have tracked the response of host and transplanted NSCs to brain or spinal cord injury and explored the therapeutic potential of NSCs injected into the animal CNS subjected to focal hypoxic-ische-mic (HI) brain or spinal cord injury. Such cells integrated appropriately into the degenerating CNS, showed robust engraftment and foreign gene expression within the region of CNS injury, and appeared to have migrated preferentially to the site of injury, experienced limited proliferation, and differentiated into neural cells lost to injury, trying to repopulate the damaged CNS area. The transplantation of exogenous NSCs may, in fact, augment a natural self-repair process in which the damaged CNS "attempts" to mobilize its own pool of stem cells. Providing additional NSCs and trophic factors may optimize this response. Therefore, NSCs may provide a novel approach to reconstituting CNS damaged by HI brain or spinal cord injury. Preliminary data in animal models of hypoxic-ischemic brain injury or contusive spinal cord injury lend support to these hypotheses.
Animals ; Brain ; Brain Injuries ; Gene Expression ; Genetic Therapy ; Models, Animal ; Neural Stem Cells* ; Neurons ; Spinal Cord Injuries ; Stem Cells ; Transplants

Recent attention has focused on the use of stem cells for therapy following ischemic stroke. Our understanding of brain injury following ischemic stroke has benefitted from a number of studies elucidating the causes and pathways leading to neuronal injury and death after anoxic insult. Other paths of research have provided the technology to create and manipulate stem cells along specific neuronal pathways. Therefore, researchers and clinicians have begun basic studies in the use of stem cell therapies to limit injury to the central nervous system and repair and regenerate injured neural tissues following hypoxia due to stroke. These therapies are showing promise and potential in improving the outcome of the stroke patient. This review covers our current knowledge and views concerning mechanisms of tissue damage following ischemic stroke, and the mechanisms by which stem cell therapy is predicted to benefit patients facing potential brain damage and loss of function. Recent reports of clinical trials using stem cells for stroke therapy are evaluated and critical points requiring further work and research are discussed.
Anoxia ; Brain ; Brain Injuries ; Brain Ischemia ; Central Nervous System ; Humans ; Neurons ; Stem Cells ; Stroke

The cerebral contusion(necrotic brain tissue infiltrated with blood) is common post-traumatic lesion, In 851 consecutive C-T scan performed by 48 hours from injury, the contusion were present in 193(22.%) of the case. Comparing the midline shift, area, number, size of the lesions and their etiopathogenesis with the clinical course(assessed by Glasgow coma scale), it is possible to evaluate the early prognosis. The patient who showed 1) midline shift over 15mm, 2) the contusional lesion in basal ganglia, brain stem or corpus callosum, 3) multiple or large sized lesion took poor prognosis. Cortical contusion especially in the frontal region had relatively good prognosis. The pathogenetic mechanisms(angular acceleration of the brain) is the same in basal ganglia, brain stem and corpus callosum, but a direct impact of the In conclusion, the etiopathogenetic mechanism and consequent site of the cerebral contusion are the most important factors on the evaluation of the severity of the brain damage and their prognosis.
Acceleration ; Basal Ganglia ; Brain ; Brain Injuries ; Brain Stem ; Coma ; Contusions* ; Corpus Callosum ; Humans ; Prognosis

In the last decade Computed Tomography(CT) has played a critical role in the diagnostic evaluation of the patients with focal brain injury. But it is apparent from pathologic studies that CT underestimates the severity of the many forms of cerebral injury such as primary brain stem injury, non-hemorrhagic cortical contusion and diffuse axonal injury(DAI). Magnetic Resonance Imaging(MRI), however, has been shown to be highly sensitive in detecting diffuse brain injury(DBI). Among the consecutive 13 cases of DBI patients in this series for 10 months, twelve patients were verified as MR evidence of injury in prospective studies. The anatomical distribution of the injuries were 11 cases of corpus callosal lesion, 6 cases of lobar white matter lesion, 1 case of primary brain stem lesion. The sensitivities of MR imaging in detecting the primary lesion were 76.9%(10/13) in T1WI and 92.3%(12/13) in T2WI. In DBI, patients with callosal injuries had higher incidence(8/12) than lobar white matter and primary brain stem lesion, the corpus callosal atrophy by midsaggital MR imaging and behavioral seguellae in survivous of severe head injury implicate the corpus callosal injury and degeneration. More accurate detection and delineation of traumatic lesions with MR should permit more accurate prediction of neurologic and cognitive recovery and assist in optimizing form of treatment.
Atrophy ; Axons ; Brain ; Brain Injuries* ; Brain Stem ; Craniocerebral Trauma ; Humans ; Magnetic Resonance Imaging* ; Prospective Studies

Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations. In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBI in the future.
Blood-Brain Barrier ; Brain Injuries ; physiopathology ; therapy ; Endothelial Cells ; cytology ; Humans ; Neurogenesis ; Stem Cells ; physiology

Cerebral somatosensory evoked potentials(SEPs) produced by stimulation of peripheral nerves provide a useful diagnostic index of conduction in somatosensory pathways to the cortex. Thus the integrity of both the dorsal column-medial lemniscus pathway and primary sensorimotor area has been considered an essential requirement to record a normal SEP. There are suggestions that SEPs contain several components arising from different neuronal sources, the early short latency potentials corresponding to the lemniscus-mediated responses and the late waves to the diffuse spino-thalamic projections. The present work analyses the influence on SEPs of focal brain lesions, using the computerized tomography in detecting and localizing brain lesions. Somatosensory evoked potentials were recorded in 20 patients with focal brain lesions recognized by computerized tomography. 1) Patients with primary sensorimotor area(PSMA) damages(group I) had a very abnormal of the early component(No, Po, Nl, Pl) in 100% on the lesion side. 2) Patients presented supratentorial lesions, sparing PSMA(group II), 87.5% showing abnormal SEPs in early components and characterized by increment of amplitude in late components. 3) Brainstem damage(group III) produced a distortion of the early components especially N11, N20msec in latency. 4) In incomplete spinal cord injuries, the SEPs is indeed signal of functional recovery, of posterior column, and incorrespondance with clinical improvement.
Brain Stem ; Brain* ; Evoked Potentials, Somatosensory* ; Humans ; Neurons ; Peripheral Nerves ; Spinal Cord Injuries

Neurologic deficits resulting from stroke remain largely intractable, which has prompted thousands of studies aimed at developing methods for treating these neurologic sequelae. Endogenous neurogenesis is also known to occur after brain damage, including that due to cerebral infarction. Focusing on this process may provide a solution for treating neurologic deficits caused by cerebral infarction. The phosphatidylinositol-3-kinase (PI3K) pathway is known to play important roles in cell survival, and many studies have focused on use of the PI3K pathway to treat brain injury after stroke. Furthermore, since the PI3K pathway may also play key roles in the physiology of neural stem cells (NSCs), eliciting the appropriate activation of the PI3K pathway in NSCs may help to improve the sequelae of cerebral infarction. This review describes the PI3K pathway, its roles in the brain and NSCs after cerebral infarction, and the therapeutic possibility of activating the pathway to improve neurologic deficits after cerebral infarction.
Brain Injuries ; Brain* ; Cell Survival ; Cerebral Infarction* ; Neural Stem Cells* ; Neurogenesis ; Neurologic Manifestations ; Physiology ; Regeneration* ; Stroke

OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.
Rats ; Animals ; Metabolomics/methods* ; Brain Injuries ; Biomarkers/metabolism* ; Brain Stem/metabolism*

The location and morphology of astrocytes are known to contribute to their diversity, and this diversity is often associated with their selective functions. However, molecular markers for astrocyte subtypes are largely unknown. In this study, we found that the immunoreactivity for glycoprotein GPM6B (M6B-IR) is preferentially expressed in the astrocytes associated with ventricles or neurogenic regions of the adult mouse brain. In particular, M6B-IR in the neurogenic niche was confined to glial fibrillary acidic protein- or nestin-expressing neural stem cells. Furthermore, in the injury penumbra, reactive astrocytes expressing nestin also exhibited strong M6B-IR. These results reveal that GPM6B is a potential molecular marker for a subset of astrocytes, as well as for the injury-dependent activation of astrocytes.
Adult ; Animals ; Astrocytes ; Brain ; Brain Injuries* ; Glycoproteins* ; Humans ; Mice* ; Nestin ; Neural Stem Cells ; Neurogenesis ; Neuroglia* ; Stem Cells