Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16 weeks post injury. At 12 weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16 weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.

• Klíčová slova
• CST, PI3K, axon regeneration, c-Fos, electrophysiology, pS6, signaling, skilled paw reaching, spinal cord, spinal cord injury,
• MeSH
• axony metabolismus   fyziologie   MeSH
• Dependovirus genetika   MeSH
• fosfatidylinositol-3-kinasy třídy I metabolismus   genetika   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• genetické vektory genetika   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• neurony metabolismus   MeSH
• obnova funkce MeSH
• poranění míchy * metabolismus   terapie   genetika   MeSH
• pyramidové dráhy * metabolismus   MeSH
• regenerace nervu * MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy třídy I MeSH
• fosfatidylinositol-3-kinasy MeSH

Adeno-associated viral vectors are widely used as vehicles for gene transfer to the nervous system. The promoter and viral vector serotype are two key factors that determine the expression dynamics of the transgene. A previous comparative study has demonstrated that AAV1 displays efficient transduction of layer V corticospinal neurons, but the optimal promoter for transgene expression in corticospinal neurons has not been determined yet. In this paper, we report a side-by-side comparison between four commonly used promoters: the short CMV early enhancer/chicken β actin (sCAG), human cytomegalovirus (hCMV), mouse phosphoglycerate kinase (mPGK) and human synapsin (hSYN) promoter. Reporter constructs with each of these promoters were packaged in AAV1, and were injected in the sensorimotor cortex of rats and mice in order to transduce the corticospinal tract. Transgene expression levels and the cellular transduction profile were examined after 6 weeks. The AAV1 vectors harbouring the hCMV and sCAG promoters resulted in transgene expression in neurons, astrocytes and oligodendrocytes. The mPGK and hSYN promoters directed the strongest transgene expression. The mPGK promoter did drive expression in cortical neurons and oligodendrocytes, while transduction with AAV harbouring the hSYN promoter resulted in neuron-specific expression, including perineuronal net expressing interneurons and layer V corticospinal neurons. This promoter comparison study contributes to improve transgene delivery into the brain and spinal cord. The optimized transduction of the corticospinal tract will be beneficial for spinal cord injury research.

• MeSH
• Dependovirus * genetika   MeSH
• genetické vektory genetika   MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• promotorové oblasti (genetika) MeSH
• pyramidové dráhy * MeSH
• transdukce genetická MeSH
• transgeny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: We aimed to produce a detailed neuropathological analysis of pyramidal motor system pathology and provide its clinical pathological correlation in cases with definite progressive supranuclear palsy (PSP). METHODS: Pyramidal motor system pathologies were analyzed in 18 cases with neuropathologically confirmed PSP. Based on a retrospective clinical analysis, cases were subtyped according to Movement Disorder Society criteria for clinical diagnosis of PSP as probable, possible or suggestive of PSP with Richardson's syndrome (n = 10), PSP with predominant corticobasal syndrome (n = 3), PSP with predominant parkinsonism (n = 3), PSP with predominant speech/language disorder (n = 1), and PSP with progressive gait freezing (n = 1). Clinical manifestations of motor neuron involvement (pseudobulbar or bulbar signs and spasticity) were retrospectively assessed semiquantitatively. Neuropathologically, hyperphosphorylated tau-related pyramidal motor system neuronal, neuritic, and glial pathology using anti-tau AT8 clone immunohistochemistry, was also evaluated. RESULTS: Clinical manifestations of pyramidal motor system involvement were found in patients with different PSP subtypes. A statistically significant higher load of tau pathology was found in the pyramidal system in PSP-Richardson's syndrome compared to other PSP subtypes (p = 0.016); however, there was no significant correlation between pyramidal system tau pathology and related motor clinical symptoms. CONCLUSIONS: Tau pathology in the spinal cord and pyramidal motor system structures is very common in progressive supranuclear palsy and may neuropathologically supplement the distinction between classic Richardson's syndrome from other progressive supranuclear palsy subtypes.

• Klíčová slova
• Atypical parkinsonism, Progressive supranuclear palsy, Spinal cord, Tauopathies,
• MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozková kůra patologie   MeSH
• parkinsonské poruchy diagnóza   patologie   MeSH
• pohybové poruchy diagnóza   patologie   MeSH
• progresivní supranukleární obrna diagnóza   patologie   MeSH
• proteiny tau metabolismus   MeSH
• pyramidové dráhy patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• MAPT protein, human MeSH Prohlížeč
• proteiny tau MeSH

BACKGROUND: TDP-43 proteinopathies represent a spectrum of neurodegenerative disorders. Variable clinical presentations including frontotemporal dementia, amyotrophic lateral sclerosis (ALS) and mixed forms are associated with the spatial heterogeneity of the TDP-43 pathology. Recent studies have emphasized the role of oligodendrocytes in the pathogenesis of ALS. OBJECTIVE: To evaluate whether TDP-43 proteinopathies are associated with an oligodendroglial response. METHODS: We performed a study on 7 controls and 10 diseased patients with spinal cord involvement. Using the oligodendroglia-specific antibody TPPP/p25, we assessed oligodendrocyte density in the lateral corticospinal tracts (LCSs) along with the presence of perineuronal oligodendrocytes (PNOGs) in the anterior horns. We performed a densitometry of myelin basic protein (MBP) immunoreactivity. The numbers of TDP-43 and p62 immunoreactive inclusions were counted in both the LCSs and the anterior horns. RESULTS: Double immunolabeling confirmed that oligodendrocytes harbor TDP-43 inclusions. In the LCSs, MBP density, but not the number of oligodendrocytes, was decreased in the diseased group. However, oligodendrocyte counts in the LCS correlated positively, and the density of MBP inversely, with the number of neuronal inclusions in the anterior horn, suggestive of a compensatory response of oligodendrocytes. The number of neurons with PNOGs correlated with the amount of inclusions. CONCLUSION: Our study further emphasizes the importance of oligodendroglia in the pathogenesis of TDP-43 proteinopathies with spinal cord involvement.

• MeSH
• buněčná inkluze metabolismus   patologie   MeSH
• buňky předních rohů míšních metabolismus   patologie   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• dospělí MeSH
• encefalitogenní základní proteiny metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mícha metabolismus   patologie   MeSH
• mladý dospělý MeSH
• motorické neurony metabolismus   patologie   MeSH
• oligodendroglie metabolismus   patologie   MeSH
• proteinopatie TDP-43 metabolismus   patologie   MeSH
• proteiny vázající RNA metabolismus   MeSH
• pyramidové dráhy metabolismus   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• encefalitogenní základní proteiny MeSH
• MBP protein, human MeSH Prohlížeč
• P62 protein, human MeSH Prohlížeč
• proteiny vázající RNA MeSH
• TARDBP protein, human MeSH Prohlížeč

BACKGROUND: Primary brain tumors in motor eloquent areas are associated with high-risk surgical procedures because of potentially permanent and often disabling motor deficits. Intraoperative primary motor cortex mapping and corticospinal tract (CST) monitoring are well-developed and reliable techniques. Imaging of the CST by diffusion tensor tractography (DTT) is also feasible. OBJECTIVE: To evaluate the practical value of 3.0T intraoperative MRI (iMRI) with intraoperative DTT (iDTT) in surgery close to the CST, and to compare high-field iDTT with intraoperative neurophysiological CST mapping during glioma and metastasis resection in a routine setting. METHODS: Twenty-five patients (13 males, 12 females, median 47 years) were enrolled prospectively from June 2010 to June 2012. Patients were included if they had a solitary supratentorial intracerebral lesion compressing or infiltrating the CST according to preoperative MRI. Subcortical CST mapping was performed by monopolar (cathodal) stimulation (500 Hz, 400 μs, 5 pulses). CST DTT was made both at preoperative and intraoperative 3.0T MRI. Subcortical motor-evoked potential threshold current and probe-CST distance were recorded at 155 points before and at 103 points after iMRI. Current-distance correlations were performed both for pre-iMRI and for post-iMRI data. RESULTS: The correlation coefficient pre-iMRI was R = 0.470 (P < .001); post-iMRI, the correlation coefficient was R = 0.338 (P < .001). MRI radical resection was achieved in 17 patients (68%), subtotal in 5 (24%), and partial in 3 (12%). Postoperative paresis developed in 8 patients (32%); the paresis was permanent in 1 case (4%). CONCLUSION: The linear current-distance correlation was found both in pre-iMRI and in post-iMRI data. Intraoperative image distortion appeared in 36%. Neurophysiological subcortical mapping remains superior to DTT. Combining these 2 methods in selected cases can help increase the safety of tumor resection close to the CST.

• MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• evokované potenciály fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku * MeSH
• mladý dospělý MeSH
• nádory mozku diagnóza   chirurgie   MeSH
• neurochirurgické výkony MeSH
• peroperační monitorování * MeSH
• pyramidové dráhy patologie   MeSH
• senioři MeSH
• svalová síla fyziologie   MeSH
• zobrazování difuzních tenzorů * MeSH
• zobrazování trojrozměrné MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Diffusion tensor imaging (DTI) is now widely used in neurosurgery to preoperatively delineate the course of the pyramidal tract. OBJECTIVE: To evaluate the accuracy of the method by comparison with subcortical electrical stimulation and to evaluate the influence of the distance of the pyramidal tract from the tumor on the resection extent and postoperative clinical deficits. METHODS: A diffusion tensor imaging depiction of the pyramidal tract was used in preoperative planning and intraoperative navigation in 72 cases. In 36 cases, subcortical electrical stimulation was used during the resection. The preoperative tumor-to-tract distance was compared with the stimulation result, the extent of resection, and the short-term postoperative course. RESULTS: A significant nonlinear relationship between the tract-to-tumor distance and the probability of a motor response to subcortical stimulation was observed. The largest preoperatively measured tumor-to-tract distance with a positive stimulation result was 8 mm. Moreover, we observed a trend toward transient postoperative motor deterioration in patients with tumors close to the pyramidal tract. Resection extent was not significantly affected by the tumor-to-tract distance. CONCLUSION: Despite methodological obstacles, reasonable accuracy of the diffusion tensor imaging reconstructions of the pyramidal tracts was confirmed by our study. The occurrence of transient postoperative motor deterioration is higher in patients with tumors located close to the pyramidal tract.

• MeSH
• difuzní magnetická rezonance metody   MeSH
• elektrodiagnostika metody   MeSH
• hluboká mozková stimulace metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mozku patologie   chirurgie   MeSH
• předoperační péče metody   MeSH
• pyramidové dráhy patologie   MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: The anatomy and somatotopy of the pyramidal tract during its course in the internal capsule has recently been discussed by many publications. However, the reports on the anatomy of the clinically more important supraventricular portion of the tract are scarce. The objective of this study is to investigate the anatomy and somatotopy of the supraventricular portion of the pyramidal tract. METHODS: In 13 patients undergoing surgery with subcortical electric stimulation for tumors located in the supraventricular white matter close to the pyramidal tract (as depicted by diffusion tensor tracking [DTT]), the relationship between the position of the stimulation point and the motor response in the arm or leg was analyzed. Additionally, the somatotopic organization of the tract was studied using separate tracking of arm and leg fibers in 20 healthy hemispheres. Finally, the course of the tract was studied by dissecting 15 previously frozen human hemispheres. RESULTS: In most cases, subcortical stimulation during the resection of tumors located behind and in front of the pyramidal tract elicited leg and arm movement, respectively. This association of stimulation point position with motor response type was significant. A DTT study of the somatotopy demonstrated a varying degree of rotation of the leg and arm fibers from mediolateral to posteroanterior configuration. Anatomic dissections demonstrated a folding-fan like structure of the pyramidal tract with a similar rotation pattern. CONCLUSION: The pyramidal tract undergoes a large part of its rotation from mediolateral to posteroanterior configuration during its course in the supraventricular white matter, although interindividual differences exist.

• MeSH
• capsula interna anatomie a histologie   fyziologie   chirurgie   MeSH
• lidé MeSH
• mapování mozku metody   MeSH
• nádory mozku chirurgie   MeSH
• neuroanatomie metody   MeSH
• pyramidové dráhy anatomie a histologie   fyziologie   chirurgie   MeSH
• retrospektivní studie MeSH
• zobrazování difuzních tenzorů metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: The paper focuses on the use of diffusion tensor imaging (DTI) in the evaluation of one case of Chiari III malformation. CASE REPORT: In the case discussed, DTI was used to delineate the position of large descending tracts within the malformation and the reconstructed images were used to plan the surgical procedure. DISCUSSION: The clinical and imaging findings, the technical aspects of the DTI fiber tract reconstruction and the outcome are summarized.

• MeSH
• Arnoldův-Chiariho syndrom patologie   chirurgie   MeSH
• difuzní magnetická rezonance MeSH
• encefalokéla patologie   chirurgie   MeSH
• fatální výsledek MeSH
• lidé MeSH
• nervová tkáň patologie   chirurgie   MeSH
• neurochirurgické výkony MeSH
• novorozenec MeSH
• počítačové zpracování obrazu MeSH
• pyramidové dráhy abnormality   patologie   chirurgie   MeSH
• ventrikuloperitoneální zkrat MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Central motor conduction time (CMCT) is usually abnormally prolonged in leg muscles of patients with pure hereditary spastic paraparesis (PHSP). One consequence of such abnormality should be an abnormal timing in the modulation of segmental reflexes, which might be more relevant for the pathophysiology of spasticity-related gait disturbances than just the CMCT delay. We examined the effects of transcranial magnetic stimulation (TMS) on the soleus H reflex in 13 control subjects and 11 PHSP patients using a conditioning (TMS) and test (H reflex) paradigm. Interstimulus interval (ISI) was 0-100 ms in steps of 10 ms. The amplitude of the H reflex at each interval was expressed as percentage of the control H reflex and the conditioned curves were compared between control subjects and patients. In control subjects, TMS-induced facilitation of the H reflex with two well-defined phases: early (ISIs 10 and 20 ms) and late (ISIs 70-90 ms). In patients, the early phase of facilitation was significantly reduced, while there was facilitation at 40 ms that was not present in control subjects. However, neither the characteristics of the MEP nor the differential modulation of the H reflex correlated significantly with clinical measures of motor dysfunction. Our results indicate an abnormal effect of TMS on the H reflex in PHSP patients. This suggests that the excitability of interneurons and soleus motoneurons is not modified in tune with the arrival of descending inputs. Desynchronization of the descending volley may contribute to both the lack of early facilitation and the presence of abnormal facilitatory phases.

• MeSH
• chůze (způsob) fyziologie   MeSH
• dospělí MeSH
• elektrická stimulace MeSH
• elektrofyziologie MeSH
• H-reflex fyziologie   MeSH
• kosterní svaly patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervus tibialis fyziologie   MeSH
• pyramidové dráhy patofyziologie   MeSH
• spastická paraparéza patofyziologie   MeSH
• transkraniální magnetická stimulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Implantation of an embryonal hippocampal tissue suspension into the area of the kainic acid lesion brought about an increase of the number of neurons. These neurons formed dendritic trees of an irregular pattern. Only neurons located within the pyramidal layer had the typical arrangement of pyramidal cells, but their dendrites were shorter and less branched.

• MeSH
• dendrity fyziologie   ultrastruktura   MeSH
• hipokampus cytologie   fyziologie   transplantace   MeSH
• inbrední kmeny potkanů MeSH
• krysa rodu Rattus MeSH
• kyselina kainová toxicita   MeSH
• neurony cytologie   fyziologie   MeSH
• plod MeSH
• přežívání štěpu MeSH
• pyramidové dráhy cytologie   patologie   fyziologie   MeSH
• transplantace fetální tkáně fyziologie   MeSH
• transplantace mozkové tkáně fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina kainová MeSH