Transplanted Embryonic Neurons Improve Functional Recovery by Increasing Activity in Injured Cortical Circuits

2020 ◽  
Vol 30 (8) ◽  
pp. 4708-4725
Author(s):  
Evgenia Andreoli ◽  
Volodymyr Petrenko ◽  
Paul Eugène Constanthin ◽  
Alessandro Contestabile ◽  
Riccardo Bocchi ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Pyramidal Neurons ◽  
Functional Integration ◽  
Epileptic Seizures ◽  
Behavioral Tests ◽  
Cortical Circuits ◽  
Functional Deficits ◽  
Promising Strategy ◽  
Neuronal Precursors

Abstract Transplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration. These heterotopic neuronal clusters significantly enhance the activity of the host circuits without causing epileptic seizures and attenuate the apoptotic injury-induced functional deficits in electrophysiological and behavioral tests. Chemogenetic activation of grafted neurons further improved functional recovery, and the persistence of the graft was necessary for maintaining restored functions in adult animals. Thus, implanting neuronal precursors capable to form synaptically integrated neuronal clusters combined with activation-based approaches represents a useful strategy for helping long-term functional recovery following brain injury.

scholarly journals An increase in dendritic plateau potentials is associated with experience-dependent cortical map reorganization

2020 ◽  
Author(s):  
Stéphane Pages ◽  
Nicolas Chenouard ◽  
Ronan Chéreau ◽  
Vladimir Kouskoff ◽  
Frédéric Gambino ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Neurons ◽  
Higher Order ◽  
Cortical Circuits ◽  
Plateau Potentials ◽  
Sensory Map ◽  
Whisker Map ◽  
Cortical Map ◽  
Cortical Representations

ABSTRACTThe organization of sensory maps in the cerebral cortex depends on experience, which drives homeostatic and long-term synaptic plasticity of cortico-cortical circuits. In the mouse primary somatosensory cortex (S1) afferents from the higher-order, posterior medial thalamic nucleus (POm) gate synaptic plasticity in layer (L) 2/3 pyramidal neurons via disinhibition and the production of dendritic plateau potentials. Here we address whether these thalamocortically mediated responses play a role in whisker map plasticity in S1. We find that trimming all but two whiskers causes a partial fusion of the representations of the two spared whiskers, concomitantly with an increase in the occurrence of POm-driven, N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials. Blocking the plateau potentials restores the archetypical organization of the sensory map. Our results reveal a novel mechanism for experience-dependent cortical map plasticity in which higher-order thalamocortically mediated plateau potentials facilitate the fusion of normally segregated cortical representations.

scholarly journals An increase in dendritic plateau potentials is associated with experience-dependent cortical map reorganization

2021 ◽  
Vol 118 (9) ◽  
pp. e2024920118
Author(s):  
Stéphane Pagès ◽  
Nicolas Chenouard ◽  
Ronan Chéreau ◽  
Vladimir Kouskoff ◽  
Frédéric Gambino ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Neurons ◽  
Higher Order ◽  
Cortical Circuits ◽  
Plateau Potentials ◽  
Sensory Map ◽  
Whisker Map ◽  
Cortical Map ◽  
Cortical Representations

The organization of sensory maps in the cerebral cortex depends on experience, which drives homeostatic and long-term synaptic plasticity of cortico-cortical circuits. In the mouse primary somatosensory cortex (S1) afferents from the higher-order, posterior medial thalamic nucleus (POm) gate synaptic plasticity in layer (L) 2/3 pyramidal neurons via disinhibition and the production of dendritic plateau potentials. Here we address whether these thalamocortically mediated responses play a role in whisker map plasticity in S1. We find that trimming all but two whiskers causes a partial fusion of the representations of the two spared whiskers, concomitantly with an increase in the occurrence of POm-driven N-methyl-D-aspartate receptor-dependent plateau potentials. Blocking the plateau potentials restores the archetypical organization of the sensory map. Our results reveal a mechanism for experience-dependent cortical map plasticity in which higher-order thalamocortically mediated plateau potentials facilitate the fusion of normally segregated cortical representations.

Prognostic value of cognitive functioning for global functional recovery in first-episode schizophrenia

2009 ◽  
Vol 40 (6) ◽  
pp. 935-944 ◽  
Author(s):  
C. González-Blanch ◽  
R. Perez-Iglesias ◽  
G. Pardo-García ◽  
J. M. Rodríguez-Sánchez ◽  
O. Martínez-García ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Functional Recovery ◽  
Negative Symptoms ◽  
First Episode ◽  
Occupational Outcomes ◽  
Functional Deficits ◽  
Logistic Regression Method ◽  
First Episode Schizophrenia

BackgroundIt has become widely accepted that cognitive deficits in schizophrenia are related to functional outcome. However, it remains to be seen whether these associations are relevant for predicting which cases will have a global functional recovery. In this study, we attempt to determine whether global functional recovery (integrating social and occupational outcomes) after first-episode schizophrenia (FES) can be predicted by cognitive variables.MethodA total of 131 FES patients with functional deficits (n=97) and functional recovery (n=34) as determined at 1-year follow-up were examined. Neuropsychological, sociodemographic, pre-morbid and clinical data at baseline were analysed using independent groups comparisons and a logistic regression method.ResultsSustained attention and negative symptoms emerged as significant predictors of good global functional outcome. Although the model revealed a high accuracy (91%) in the classification of patients with functional deficits, it was unacceptably low (26%) in the classification of patients with global functional recovery.ConclusionsThe limitations found in the prediction of a favourable global functional outcome may well be an indication for a need to address the role of other factors not commonly included in longitudinal studies of long-term outcomes in schizophrenia.

The use of progesterone during pregnancy in women with epilepsy as an alternative to the correction of doses of anticonvulsants

GYNECOLOGY ◽  
2020 ◽  
Vol 21 (6) ◽  
pp. 12-15
Author(s):  
Elena V. Tsallagova ◽  
Vasily O. Generalov ◽  
Timur R. Sadykov
Keyword(s):  
Clinical Remission ◽  
Epileptic Seizures ◽  
Progesterone Concentration ◽  
Teratogenic Effects ◽  
Safe Alternative ◽  
Patients With Epilepsy

Pregnancy is the most dangerous period in terms of interruption of even persistent and long-term remission. At the same time increasing the dose of anticonvulsant increases the risk of teratogenic effects. Aim. to assess the possibility of using progesterone to prevent relapse of epileptic seizures during pregnancy. Materials and methods. 38 pregnant patients with epilepsy with clinical remission before pregnancy, with relapse of epileptic seizures in I trimester of pregnancy, age 31.81.4 years. Dydrogesterone in a dose of 10 to 60 mg/day was prescribed after the relapse of remission. Anticonvulsant dosage was not changed. The blood progesterone concentration and EEG control was carried out. Results. During pregnancy, the level of progesterone in the blood gradually increased from 77.8 nmol/l at 78 weeks of pregnancy to 521.1 nmol/l at 3637 weeks of pregnancy, without exceeding the limits. EEG results did not deteriorate. None of the patients had seizures during pregnancy. Conclusion. Progesterone therapy is an adequate and safe alternative to increasing the dose of anticonvulsants in case of recurrent seizures during pregnancy.

ECG-Patterns of Focal Epileptic Seizures, the Role in Sudden Unexpected Death in Epilepsy: A Prospective Long-Term Study

2019 ◽  
Author(s):  
Svetlana Serdyuk ◽  
Karapet V. Davtyan ◽  
Sergey G. Burd ◽  
Oksana M. Drapkina ◽  
Sergey A. Boytsov ◽  
...  
Keyword(s):  
Epileptic Seizures ◽  
Sudden Unexpected Death ◽  
Unexpected Death ◽  
Term Study ◽  
Long Term Study

Chinese Medicine Protein and Peptide in Gene and Cell Therapy

2019 ◽  
Vol 20 (3) ◽  
pp. 251-264 ◽  
Author(s):  
Yinlu Feng ◽  
Zifei Yin ◽  
Daniel Zhang ◽  
Arun Srivastava ◽  
Chen Ling
Keyword(s):  
Chinese Medicine ◽  
Cell Therapy ◽  
Future Research ◽  
The Past ◽  
Promising Strategy ◽  
Wide Range ◽  
New Directions ◽  
Gene And Cell Therapy ◽  
Proteins And Peptides

The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers. More recently, they have been utilized in gene and cell therapy, resulting in promising novel strategies to treat both cancer and non-cancer diseases. This manuscript presents a critical review on this field, accompanied with perspectives on the challenges and new directions for future research in this emerging frontier.

Regulation of apoptosis in adipocytes and breast cancer cells by 1,25-dihydroxyvitamin D3: a link between obesity and breast cancer

2013 ◽  
Vol 14 (3) ◽  
Author(s):  
Igor N. Sergeev
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Cancer ◽  
Tissue Mass ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
Promising Strategy ◽  
Adipose Tissue Mass

AbstractModulation of apoptosis is emerging as a promising strategy for prevention and treatment of breast cancer and obesity because removal of mammary cancer cells and mature adipocytes through this process will result in decreasing tumor size and produce long-term reduction in adipose tissue mass. The hormone 1,25-dihydroxyvitamin D

Predictors of functional recovery following surgery for foot drop due to degenerative lumbar disease

2021 ◽  
pp. 1-6
Author(s):  
Assaf Berger ◽  
Laurence Mangel ◽  
Sharif Basal ◽  
Zvi Lidar ◽  
Gilad J Regev ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Postoperative Period ◽  
Univariate Analysis ◽  
Degenerative Disease ◽  
Foot Drop ◽  
Functional Improvement ◽  
Lumbar Degenerative Disease ◽  
Motor Weakness ◽  
Short And Long Term

OBJECTIVE Surgery for foot drop secondary to lumbar degenerative disease is not always associated with postoperative functional improvement. It is still unclear whether early decompression results in better functional recovery and how soon surgery should be performed. This study aimed to evaluate predicting factors that affect short- and long-term recovery outcomes and to explore the relationship between timing of lumbar decompression and recovery from foot drop in an attempt to identify a cutoff time from symptom onset until decompression for optimal functional improvement. METHODS The authors collected demographic, clinical, and radiographic data on patients who underwent surgery for foot drop due to lumbar degenerative disease. Clinical data included tibialis anterior muscle (TAM) strength before and after surgery, duration of preoperative motor weakness, and duration of radicular pain until surgery. TAM strength was recorded at the immediate postoperative period and 1 month after surgery while long-term follow-up on functional outcomes were obtained at ≥ 2 years postsurgery by telephone interview. Data including degree and duration of preoperative motor weakness as well as the occurrence of pain and its duration were collected to analyze their impact on short- and long-term outcomes. RESULTS The majority of patients (70%) showed functional improvement within 1 month postsurgery and 40% recovered to normal or near-normal strength. Univariate analysis revealed a trend toward lower improvement rates in patients with preoperative weakness of more than 3 weeks (33%) compared with patients who were operated on earlier (76.5%, p = 0.034). In a multivariate analysis, the only significant predictor for maximal strength recovery was TAM strength before surgery (OR 6.80, 95% CI 1.38–33.42, p = 0.018). Maximal recovery by 1 month after surgery was significantly associated with sustained long-term functional improvement (p = 0.006). CONCLUSIONS Early surgery may improve the recovery rate in patients with foot drop caused by lumbar degenerative disease, yet the strongest predictor for the extent of recovery is the severity of preoperative TAM weakness. Maximal recovery in the short-term postoperative period is associated with sustained long-term functional improvement and independence.

Sign in / Sign up

Export Citation Format

Share Document