Mapping neuroplastic potential in brain-damaged patients

Herbet, Guillaume; Maheu, Maxime; Costi, Emanuele; Lafargue, Gilles; Duffau, Hugues

doi:10.1093/brain/awv394

Cited by 239 publications

(204 citation statements)

References 76 publications

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“…Accordingly, in the grid walk task we found that the recovery of motor function of affected limbs in CNF1-treated animals is accompanied by a slight improvement of the performance with unaffected limbs. Since CNF1 promotes activity-dependent plasticity in the adult cortex [15], the toxin might enhance the spontaneous remapping of motor maps in peritumoral areas [26, 27] thus leading to greater functional preservation. Moreover, CNF1 infusion induced a significant increase of PSD95 protein levels in the peritumoral area.…”

Section: Discussionmentioning

confidence: 99%

Progression of motor deficits in glioma-bearing mice: impact of CNF1 therapy at symptomatic stages

et al. 2017

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Glioblastoma (GBM) is the most aggressive type of brain tumor. In this context, animal models represent excellent tools for the early detection and longitudinal mapping of neuronal dysfunction, that are critical in the preclinical validation of new therapeutic strategies. In a mouse glioma model, we developed sensitive behavioral readouts that allow early recognizing and following neurological symptoms. We injected GL261 cells into the primary motor cortex of syngenic mice and we used a battery of behavioral tests to longitudinally monitor the dysfunction induced by tumor growth. Grip strength test revealed an early onset of functional deficit associated to the glioma growth, with a significant forelimb weakness appearing 9 days after tumor inoculation. A later deficit was observed in the rotarod and in the grid walk tasks. Using this model, we found reduced tumor growth and maintenance of behavioral functions following treatment with Cytotoxic Necrotizing Factor 1 (CNF1) at a symptomatic stage. Our data provide a detailed and precise examination of how tumor growth reverberates on the behavioral functions of glioma-bearing mice, providing normative data for the study of therapeutic strategies for glioma treatment. The reduced tumor volume and robust functional sparing observed in CNF1-treated, glioma-bearing mice strengthen the notion that CNF1 delivery is a promising strategy for glioma therapy.

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Section: Discussionmentioning

confidence: 99%

Progression of motor deficits in glioma-bearing mice: impact of CNF1 therapy at symptomatic stages

et al. 2017

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“…It has long been a fundamental issue in clinical neuro-oncology to explore the pattern of functional and structural reorganization of the brain following tumor growth (Duffau, 2014;Herbet, Maheu, Costi, Lafargue, & Duffau, 2016;Kinno, Ohta, Muragaki, Maruyama, & Sakai, 2014). Such kind of research holds vital clinical significance in either facilitating the understanding of disease-specific mechanisms in the development and prognosis of diseases, or providing new insight into therapeutic targets for novel and more effective treatment interventions.…”

Section: Introductionmentioning

confidence: 99%

Reorganization of cerebro‐cerebellar circuit in patients with left hemispheric gliomas involving language network: A combined structural and resting‐state functional MRI study

Zhang

Xia

Qiu

et al. 2018

Human Brain Mapping

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The role of cerebellum and cerebro-cerebellar system in neural plasticity induced by cerebral gliomas involving language network has long been ignored. Moreover, whether or not the process of reorganization is different in glioma patients with different growth kinetics remains largely unknown. To address this issue, we utilized preoperative structural and resting-state functional MRI data of 78 patients with left cerebral gliomas involving language network areas, including 46 patients with low-grade glioma (LGG, WHO grade II), 32 with high-grade glioma (HGG, WHO grade III/IV), and 44 healthy controls. Spontaneous brain activity, resting-state functional connectivity and gray matter volume alterations of the cerebellum were examined. We found that both LGG and HGG patients exhibited bidirectional alteration of brain activity in language-related cerebellar areas. Brain activity in areas with increased alteration was significantly correlated with the language and MMSE scores. Structurally, LGG patients exhibited greater gray matter volume in regions with increased brain activity, suggesting a structure-function coupled alteration in cerebellum. Furthermore, we observed that cerebellar regions with decreased brain activity exhibited increased functional connectivity with contralesional cerebro-cerebellar system in LGG patients. Together, our findings provide empirical evidence for a vital role of cerebellum and cerebro-cerebellar circuit in neural plasticity following lesional damage to cerebral language network. Moreover, we highlight the possible different reorganizational mechanisms of brain functional connectivity underlying different levels of behavioral impairments in LGG and HGG patients.

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“…It is possible in this case (P4) that, due to fast tumor growth, mainly suppression of functional areas occurs, whereas the integrity of white matter bundles associated with function remains intact. Herbet et al [28] showed via a probabilistic atlas that reorganization at subcortical level, in proximity to white matter tracts, could be less optimal than at cortical level. In addition, Trinh et al [29] demonstrated that a subcortical injury was an independent predictor for longer-term neurological impairments underlining the importance of preservation of subcortical tracts.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Awake Glioma Surgery in “Critical” Language Areas on Cognition: 4 Case Studies

Satoer

Witte²,

Smits

et al. 2017

Case Reports in Neurological Medicine

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Awake surgery with electrocorticosubcortical stimulation is the golden standard treatment for gliomas in eloquent areas. Preoperatively, mostly mild cognitive disturbances are observed with postoperative deterioration. We describe pre- and postoperative profiles of 4 patients (P1–P4) with gliomas in “critical” language areas (“Broca,” “Wernicke,” and the arcuate fasciculus) undergoing awake surgery to get insight into the underlying mechanism of neuroplasticity. Neuropsychological examination was carried out preoperatively (at T1) and postoperatively (at T2, T3). At T1, cognition of P1 was intact and remained stable. P2 had impairments in all cognitive domains at T1 with further deterioration at T2 and T3. At T1, P3 had impairments in memory and executive functions followed by stable recovery. P4 was intact at T1, followed by a decline in a language test at T2 and recovery at T3. Intraoperatively, in all patients language positive sites were identified. Patients with gliomas in “critical” language areas do not necessarily present cognitive disturbances. Surgery can either improve or deteriorate (existing) cognitive impairments. Several factors may underlie the plastic potential of the brain, for example, corticosubcortical networks and tumor histopathology. Our findings illustrate the complexity of the underlying mechanism of neural plasticity and provide further support for a “hodotopical” viewpoint.

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Mapping neuroplastic potential in brain-damaged patients

Cited by 239 publications

References 76 publications

Progression of motor deficits in glioma-bearing mice: impact of CNF1 therapy at symptomatic stages

Progression of motor deficits in glioma-bearing mice: impact of CNF1 therapy at symptomatic stages

Reorganization of cerebro‐cerebellar circuit in patients with left hemispheric gliomas involving language network: A combined structural and resting‐state functional MRI study

Differential Effects of Awake Glioma Surgery in “Critical” Language Areas on Cognition: 4 Case Studies

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