Midbrain injury in patients with subarachnoid hemorrhage: a diffusion tensor imaging study.

We investigated the characteristics of midbrain injuries in patients with spontaneous subarachnoid hemorrhage (SAH) by using diffusion tensor imaging (DTI). Twenty-seven patients with SAH and 25 healthy control subjects were recruited for this study. Fractional anisotropy (FA) and mean diffusivity (MD) data were obtained for four regions of the midbrain (the anterior ventral midbrain, posterior ventral midbrain, tegmentum area, and tectum) in 27 hemispheres that did not show any pathology other than SAH. The mean FA and MD values of the four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) of the patient group were significantly lower and higher than those of the control group, respectively (p < 0.05). The mean FA values of the patient group were significantly different among the anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum regions (ANOVA; F = 3.22, p < 0.05). Post hoc testing showed that the mean FA value of the anterior ventral midbrain was significantly lower than those of the posterior ventral midbrain, tegmentum, and tectum (p < 0.05); in contrast, there were no differences in mean FA values of the posterior ventral midbrain, tegmentum, and tectum (p > 0.05). However, differences were not observed among four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) in the mean MD values. We detected evidence of neural injury in all four regions of the midbrain of patients with SAH, and the anterior ventral midbrain was the most severely injured among four regions of the midbrain. Our results suggest that a pathophysiological mechanism of these neural injuries might be related to the occurrence of a subarachnoid hematoma.

TET2-mediated Cdkn2A DNA hydroxymethylation in midbrain dopaminergic neuron injury of Parkinson's disease.

It has been reported that abnormal epigenetic modification is associated with the occurrence of Parkinson's disease (PD). Here, we found that a ten-eleven translocation 2 (TET2), a staff of the DNA hydroxylases family, was increased in dopaminergic neurons in vitro and in vivo. Genome-wide mapping of DNA 5-hydroxymethylcytosine (5-hmC)-sequencing has revealed an aberrant epigenome 5-hmC landscape in 1-methyl-4-phenylpyridinium iodide (MPP+)-induced SH-SY5Y cells. The TET family of DNA hydroxylases could reverse DNA methylation by oxidization of 5-methylcytosine (5-mC) to 5-hmC. However, the relationship between modification of DNA hydroxymethylation and the pathogenesis of PD is not clear. According to the results of 5-hmC-sequencing studies, 5-hmC was associated with gene-rich regions in the genomes related to cell cycle, especially gene-cyclin-dependent kinase inhibitor 2A (Cdkn2A). Downregulation of TET2 expression could significantly rescue MPP+-stimulated SH-SY5Y cell damage and cell cycle arrest. Meanwhile, knockdown of Tet2 expression in the substantia nigra pars compacta of MPTP-induced PD mice resulted in attenuated MPTP-induced motor deficits and dopaminergic neuronal injury via p16 suppression. In this study, we demonstrated a critical function of TET2 in PD development via the CDKN2A activity-dependent epigenetic pathway, suggesting a potential new strategy for epigenetic therapy.

Use of neuron-specific enolase to predict mild brain injury in motorcycle crash patients with maxillofacial fractures: A pilot study.

PURPOSE: Mild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronal damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents. METHODS: Blood samples were drawn from 40 healthy people (control group) and 48 trauma patients who had sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed. RESULTS: The NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p < 0.001). The mean NSE serum level (ng/ml) in the lower part of the facial skeleton (15.44 with SD 15.34) was higher than that in the upper facial part (12.42 with SD 7.68); and the mean NSE level (ng/ml) in the middle-and lower part (11.97 with SD 5.63) was higher than in the middle part (7.88 with SD 2.64). CONCLUSION: An increase in NSE serum levels can be observed in patients sustained maxillofacial fractures and mild brain injury.

The acute transcriptome response of the midbrain/diencephalon to injury in the adult mummichog (Fundulus heteroclitus).

Adult fish produce new cells throughout their central nervous system during the course of their lives and maintain a tremendous capacity to repair damaged neural tissue. Much of the focus on understanding brain repair and regeneration in adult fish has been directed at regions of the brainstem and forebrain; however, the mesencephalon (midbrain) and diencephalon have received little attention. We sought to examine differential gene expression in the midbrain/diencephalon in response to injury in the adult fish using RNA-seq. Using the mummichog (Fundulus heteroclitus), we administered a mechanical lesion to the midbrain/diencephalon and examined differentially expressed genes (DEGs) at an acute recovery time of 1 h post-injury. Comparisons of whole transcriptomes derived from isolated RNA of intact and injured midbrain/diencephalic tissue identified 404 DEGs with the vast majority being upregulated. Using qPCR, we validated the upregulation of DEGs pim-2-like, syndecan-4-like, and cd83. Based on genes both familiar and novel regarding the adult brain response to injury, these data provide an extensive molecular profile giving insight into a range of cellular processes involved in the injury response of a brain regenerative-capable vertebrate.

Holmes Tremor Secondary to a Stabbing Lesion in the Midbrain.

Background: The development of Holmes tremor (HT) after a direct lesion of the midbrain has rarely been reported in the literature, although several etiologies have been linked with HT, such as stroke, brainstem tumors, multiple sclerosis, head trauma, or infections. Phenomenology Shown: A 31-year-old male, having been stabbed in the right eye, presented with a rest and action tremor in the left upper limb associated with left hemiparesis with corresponding post-contrast volumetric magnetic resonance imaging T1 with sagittal oblique reformation showing the knife trajectory reaching the right midbrain. Educational Value: Despite the rarity of the etiology of HT in the present case, clinicians working with persons with brain injuries should be aware of this type of situation.

The diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions.

The objective of this study was to investigate the diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions. A total of 63 patients (45 men and 18 women; mean age of 43 years with a range from 20 to 72 years) who suffered from traumatic bifrontal contusions between January 2007 and December 2012 were inspected. The clinical and imaging results were studied for all patients, and we found that swelling of the mesencephalon and a downward shift of the bilateral red nucleus were significant signs of central brain herniation in the image of magnetic resonance imaging. All patients were given a simultaneous bilateral craniotomy for balanced decompressive surgery. The Glasgow Outcome Scale was used to monitor the patients during the follow-up period, which lasted from 6 to 52 months with a mean of 22 months. At the termination of the follow-up period, the following Glasgow Outcome Scale scores were obtained: 14 patients scored 5 points, 22 patients scored 4 points, 7 patients scored 3 points, 13 patients scored 2 points, and 7 patients scored 1 point. Therefore, our study suggested that an early magnetic resonance imaging scan could result in a more timely diagnosis of central brain herniation, and simultaneous bilateral craniotomy was found to be one of the best treatments for central brain herniation to improve patient outcomes.

Síndrome de Percheron: Lesiones talámicas bilaterales / Percheron Syndrome: Thalamic bilateral lesions

El síndrome de Percheron o infarto talámico bilateral sincrónico se considera infrecuente y de difícil diagnóstico clínico. Presentamos el caso de un paciente con lesiones isquémicas agudas en ambos tálamos y mesencéfalo anterior, compatibles con obstrucción del la arteria de Percheron. La compleja irrigación talámica y la variabilidad individual hacen que las lesiones isquémicas puedan presentarse en forma de lesiones bilaterales y confieren importancia a este cuadro. La Resonancia Magnética cerebral (RM) es fundamental en el correcto diagnóstico

Percheron Syndrome also known as bilateral synchronic thalamic infarction is consider as an infrequent of difficult diagnosis syndrome. We describe the case of a male patient presenting acute ischemic lesions in both thalamus and anterior mesencephalon caused by an obstruction of the Percheron artery. The complexity of thalamic vascularization and individual differences make ischemic lesions appear as bilateral, tha's the importance of this syndrome. Brain MRI is proposed as fundamental for a correct diagnosis

Subarachnoid haemorrhage associated with an intrathecal catheter.

Although 15 to 20 percent of patients with subarachnoid haemorrhage (SAH) do not have a vascular lesion on four-vessel cerebral angiography, venous injury is a potential cause. This case describes an intracranial catheter associated with nonaneurysmal SAH. It suggests that intrathecal catheters can cause vascular injury, and that nonaneurysmal perimesencephalic SAH may be due to injury of small blood vessels.

Gender segregation in gene expression and vulnerability to oxidative stress induced injury in ventral mesencephalic cultures of dopamine neurons.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNC). Most epidemiologic studies have demonstrated that PD has a higher prevalence in males than in females. Both hormones and genetic factors have been considered to be contributors to this phenomenon. In the present study, we used primary cultures of ventral mesencephalic (VM) neurons from E13.5 Balb/C mice to investigate whether there were any gender differences in gene expression and cell sensitivity to oxidative stress in sex segregated cultures. We also investigated the role of SRY, the sex-determining region on the Y chromosome, and the female hormone estrogen in the gender dimorphism. We measured the expression levels of genes that previously were thought to be related to PD or DA neuron development and functions by real-time PCR, and found six of them, ATP13A2, ERß, MAO-A, D2, DAT, and Pitx3, showing significantly differential expression between males and females in the normal physiological state or under stress conditions. Furthermore, we demonstrated that male VM neurons are more vulnerable than female neurons to rotenone-induced cytotoxicity and that 17ß-estrogen has a moderate protective effect in both male and female VM neurons. Moreover, we document that SRY can upregulate monoamine oxidase A and downregulate estrogen receptor-ß, and SRY-overexpressing N2A cells enhance the resistance to oxidative stress-induced cell injury. Our results suggest that gender indeed influences several PD-related gene expressions in VM neurons, and SRY and estrogen are involved in the different responses to oxidative stress in culture.

The organization of cortical activity in the anterior lobe of the cat cerebellum during hindlimb stepping.

We recorded from over 280 single cortical neurons throughout the medial anterior lobe of the cat cerebellum during passive movements of the hindlimbs resembling stepping on a moving treadmill. We used three stepping patterns, unilateral stepping of either the ipsilateral or contralateral leg and bipedal stepping in an alternating gait pattern. We found that over 60% of the neurons, mostly Purkinje cells, responded to stepping of one or both legs, and over 40% to more than one type of stepping pattern. Responsive cells were distributed throughout the five anterior lobules, and the highest concentration was found in traditional hindlimb areas in lobules 2 and 3. A comparison of response waveforms showed that they are similar for neighboring cells in many parts of the cerebellar cortex, and they tend to form local blob-like groupings. Response patterns, i.e., relationship among responses to each stepping type, tended to be similar within a local group. The groupings extend further in the parasagittal dimension (up to about a third of a lobule) than in the transverse dimension (about 1 mm), and they may form functional modules. A principal component analysis also showed that the responses were composed of a four basis waveforms (principal components) that explained about 80% of the response waveform variance that were nearly identical to those derived from dorsal spinocerebellar tract (DSCT) responses to similar stepping movements. We reconstructed the locations of the recorded neurons on a 2D map of the cerebellar cortex showing the spatial distribution of responsive cells according to their response characteristics. We propose, on the basis of these results, that the sensory input to the cerebellum from the hindlimbs is distributed to multiple zones that may each contribute to a different component of cerebellar function.

Effects of unilateral midbrain lesions on gaze (eye and head) movements.

The rostral midbrain, especially the rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF) and the interstitial nucleus of Cajal (INC), plays an important role in the control of eye movements. Although the effect of midbrain lesions on eye movements is well investigated, little is known about its effect on head movements. In this study, we measured eye and head (gaze) movements in five patients with unilateral, acute midbrain lesions and nine healthy controls. In all patients, vertical eye velocity was reduced as a result of the lesion compared to healthy subjects, whereas peak head velocity was not affected. Further, most patients displayed an increased contralesional torsion in peripheral head positions, independently of whether they presented a head tilt in the straight-ahead position or not. Our results indicate that midbrain lesions affect the control of eye and head differently and independently.

Effects of epigallocatechin gallate on rotenone-injured murine brain cultures.

Green tea polyphenol epigallocatechin-3-gallate (EGCG) is reported to have antioxidant abilities and to counteract beneficially mitochondrial impairment and oxidative stress. The present study was designed to investigate neuroprotective effects of EGCG on rotenone-treated dissociated mesencephalic cultures and organotypic striatal cultures. Rotenone is a potent inhibitor of complex I of the respiratory chain, which in vitro causes pathological and neurochemical characteristics of diseases in which mitochondrial impairment is involved, e.g., Parkinson's disease. Treatment with EGCG (0.1, 1, 10 muM) alone had no significant effects on mesencephalic cultures. In striatal slice cultures, EGCG led to a significant increase of propidium iodide (PI) uptake and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM), but not dihydroethidium (DHE) fluorescence intensity. Rotenone (20 nM on the eighth DIV for 48 h) significantly decreased the numbers and the neurite lengths of TH ir neurons by 23 and 34% in dissociated mesencephalic cell cultures compared to untreated controls. Exposure of striatal slices to rotenone (0.5 mM for 48 h) significantly increased PI uptake, and DAF-FM and DHE fluorescence intensities by 41 and 136 and 19%, respectively, compared to controls. Against rotenone, in dissociated mesencephalic cultures, EGCG produced no significant effect on either the number or neurite lengths of THir neurons compared to rotenone-treated cultures, but EGCG significantly decreased PI uptake by 19% and DAF-FM fluorescence intensity by 19 and 58%, respectively, compared to increase in rotenone-exposed striatal slices. On the other hand, EGCG did not affect superoxide (O(2) (-)) formation as detected with DHE. These data indicate that EGCG slightly protects striatal slices by counteracting nitric oxide (NO(.)) production by rotenone. In conclusion, EGCG partially protects striatal slices but not dissociated cells against rotenone toxicity.

Kernohan's notch phenomenon in chronic subdural hematoma: MRI findings.

We report two cases of Kernohan's notch phenomenon secondary to chronic subdural hematoma detected by MRI. In the first case, the patient was drowsy with an oculomotor palsy and a hemiparesis ipsilateral to the chronic subdural hematoma. MRI in the post-operative period showed no abnormal signal or deformity of the crus cerebri. The neurological signs immediately resolved after trephination. In the second case, the patient was admitted with progressive decrease in their level of consciousness and ipsilateral hemiparesis with the chronic subdural hematoma. MRI on admission revealed an abnormal signal in the contralateral crus cerebri against the chronic subdural hematoma. After surgery, the mental state gradually recovered to normal with some degree of residual hemiparesis. In patients with chronic subdural hematoma, a compressive deformity of the crus cerebri, without abnormal signal on MRI, may predict a better neurological recovery in patients with Kernohan's notch phenomenon.

The mesencephalic trigeminal sensory nucleus is involved in acquisition of active exploratory behavior induced by changing from a diet of exclusively milk formula to food pellets in mice.

Post-weaning mice fed exclusively milk display low-frequency exploratory behavior [Ishii, T., Itou, T., and Nishimura, M. (2005) Life Sci. 78, 174-179] compared to mice fed a food pellet diet. This low-frequency exploratory behavior switched to high-frequency exploration after a switch from exclusively milk formula to a food pellet diet. Acquisition of the high-frequency exploratory behavior was irreversible. Recently, we demonstrated that the mesencephalic trigeminal nucleus (Me5) is involved in the control of feeding and exploratory behavior in mice without modulating the emotional state [Ishii, T., Furuoka, H., Itou, T., Kitamura, N., and Nishimura, M. (2005) Brain Res. 1048, 80-86]. We therefore investigated whether the Me5 is involved in acquisition of high-frequency exploratory behavior induced by the switch in diet from an exclusively milk formula to food pellets. Mouse feeding and exploratory behaviors were analyzed using a food search compulsion apparatus, which was designed to distinguish between the two behaviors under standard living conditions. Immunohistochemical analysis of immediate early genes indicated that the Me5, which receives signals from oral proprioceptors, is transiently activated after the diet change. The change from low-frequency to high-frequency exploratory behavior was prevented in milk-fed mice by bilateral lesion of the Me5. These results suggest that the Me5 is activated by signals associated with mastication-induced proprioception and contributes to the acquisition of active exploratory behavior.

Effect of 4-aminopyridine on upbeat and downbeat nystagmus elucidates the mechanism of downbeat nystagmus.

The potassium channel blocker 4-aminopyridine (4-AP) restored vertical smooth pursuit and gaze holding in light in one patient with upbeat (UBN) and in one with downbeat nystagmus (DBN). Without a visible target, however, 4-AP had no effect on UBN, but DBN vanished. We hypothesize that this difference in the effects of 4-AP, which is known to increase the excitability of cerebellar Purkinje cells, can be attributed to the different lesion sites involved in UBN and DBN.