Autologous Adult Cortical Cell Transplantation Enhances Functional Recovery Following Unilateral Lesion of Motor Cortex in Primates: A Pilot Study

Kaeser, Mélanie; Brunet, Jean‐François; Wyss, Alexander F.; Belhaj-Saïf, Abderraouf; Liu, Yu; Hamadjida, Adjia; Rouiller, Eric M.; Bloch, Jocelyne

doi:10.1227/neu.0b013e31820c02c0

Cited by 35 publications

(87 citation statements)

References 39 publications

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“…Still in monkeys (Barone and Joseph, 1989;Funahashi et al, 1993;Ninokura et al, 2004;Shima et al, 2007;Berdyyeva and Olson, 2010), a fairly comparable representation of motor sequencing was found in the dorsolateral prefrontal cortex (dlPFC). A role played by SMA in the control of motor sequences has also been found in human subjects (e.g., Gerloff et al, 1997;Boecker et al, 1998;Deiber et al, 1999;Lepage et al, 1999;Schubotz and Von Cramon, 2001;Verwey et al, 2002;Van Mier et al, 2004;Bengtsson et al, 2004;Kennerley et al, 2004;Tanaka et al, 2010).…”

Section: Introductionmentioning

confidence: 67%

“…The monkeys ranged from 2.5 to 5.5 years old at the time of initiation of behavioural training sessions. All the behavioural and surgical procedures were approved by the local ethical committee, in accordance with the Guidelines for the Care and Use of Laboratory Animals and approved by Swiss veterinary authorities (see e.g., Kaeser et al, 2010Kaeser et al, , 2011Bashir et al, 2012;Schmidlin et al, 2011). Briefly, the monkeys were trained to enter and sit into a Plexiglas primate chair (Schmidlin et al, 2011).…”

Section: Subjects and Behavioural Tasksmentioning

confidence: 99%

“…For the present investigation, the motor performances at the modified Brinkman board task e static e and the rotating Brinkman board task e moving either clockwise or counterclockwise e were analysed. These two tasks were described in more detail in previous studies (Brinkman and Kuypers, 1973;Brinkman, 1984;Liu and Rouiller, 1999;Freund et al, 2009;Kaeser et al, 2010Kaeser et al, , 2011Schmidlin et al, 2011) and can be seen on the following web page: http://www.unifr.ch/neuro/rouiller/ research/brink.php. For each monkey, the performance of the left hand and the right hand were analysed separately.…”

Section: Subjects and Behavioural Tasksmentioning

confidence: 99%

“…The surgical procedures were described in previous reports from this laboratory (Liu and Rouiller, 1999;Kaeser et al, 2010Kaeser et al, , 2011Bashir et al, 2012). Briefly, after completion of training and once the monkey reached a behavioural plateau, the animal was subjected to the following surgical procedures.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…Once the entire experiment was completed (effect of subsequent motor cortex lesion and recovery, see Bashir et al, 2012;Kaeser et al, 2010Kaeser et al, , 2011, the monkeys were sacrificed. They were first anesthetized with an intramuscular ketamine injection, and then received a lethal dose of sodium pentobarbital (90 mg/kg).…”

Section: Histology Of the Prefrontal Area After Biopsymentioning

confidence: 99%

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Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: Evidence for a contribution of the dorsolateral prefrontal cortex

Kaeser

Wannier

Brunet

et al. 2013

Cortex

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In the context of an autologous cell transplantation study, a unilateral biopsy of cortical tissue was surgically performed from the right dorsolateral prefrontal cortex (dlPFC) in two intact adult macaque monkeys (dlPFC lesioned group), together with the implantation of a chronic chamber providing access to the left motor cortex. Three other monkeys were subjected to the same chronic chamber implantation, but without dlPFC biopsy (control group). All monkeys were initially trained to perform sequential manual dexterity tasks, requiring precision grip. The motor performance and the prehension's sequence (temporal order to grasp pellets from different spatial locations) were analysed for each hand.Following the surgery, transient and moderate deficits of manual dexterity per se occurred in both groups, indicating that they were not due to the dlPFC lesion (most likely related to the recording chamber implantation and/or general anaesthesia/medication). In contrast, changes of motor habit were observed for the sequential order of grasping in the two monkeys with dlPFC lesion only. The changes were more prominent in the monkey subjected to the largest lesion, supporting the notion of a specific effect of the dlPFC lesion on the motor habit of the monkeys. These observations are reminiscent of previous studies using conditional tasks with delay that have proposed a specialization of the dlPFC for visuo-spatial working memory, except that this is in a different context of "free-will", nonconditional manual dexterity task, without a component of working memory.

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Section: Introductionmentioning

confidence: 67%

Section: Subjects and Behavioural Tasksmentioning

confidence: 99%

Section: Subjects and Behavioural Tasksmentioning

confidence: 99%

Section: Surgical Proceduresmentioning

confidence: 99%

Section: Histology Of the Prefrontal Area After Biopsymentioning

confidence: 99%

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Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: Evidence for a contribution of the dorsolateral prefrontal cortex

Kaeser

Wannier

Brunet

et al. 2013

Cortex

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Distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects

et al. 2013

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Background The present study aimed to determine and confront hand preference (hand chosen in priority to perform a manual dexterity task) and hand dominance (hand with best motor performance) in eight macaques (Macaca fascicularis) and in 20 human subjects (10 left-handers and 10 right-handers). Methods Four manual dexterity tests have been executed by the monkeys, over several weeks during learning and stable performance phases (in controlled body position): the modified Brinkman board, the reach and grasp drawer, the tube and the bimanual board tasks. Three behavioral tests, adapted versions from the monkeys tasks (modified Brinkman board, tube and bimanual board tasks), as well as a handedness questionnaire, have been conducted in human subjects. Results In monkeys, there was a large disparity across individuals and motor tasks. For hand dominance, two monkeys were rather right lateralized, three monkeys rather left lateralized, whereas in three monkeys, the different parameters measured were not consistent. For hand preference, none of the eight monkeys exhibited a homogeneous lateralization across the four motor tasks. Macaca fascicularis do not exhibit a clear hand preference. Furthermore, hand preference often changed with task repetition, both during training and plateau phases. For human subjects, the hand preference mostly followed the self-assessment of lateralization by the subjects and the questionnaire (in the latter, right-handers were more lateralized than left-handers), except a few discrepancies based on the tube task. There was no hand dominance in seven right-handers (the other three performed better with the right hand) and in four left-handers. Five left-handers showed left-hand dominance, whereas surprisingly, one left-hander performed better with the right hand. In the modified Brinkman board task, females performed better than males, right-handers better than left-handers. Conclusions The present study argues for a distinction between hand preference and hand dominance, especially in macaque monkeys.

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Primate adult brain cell autotransplantation produces behavioral and biological recovery in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced parkinsonian St. Kitts monkeys

Bloch

Brunet

McEntire

et al. 2014

J of Comparative Neurology

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The potential for "replacement cells" to restore function in Parkinson's disease has been widely reported over the past 3 decades, rejuvenating the central nervous system rather than just relieving symptoms. Most such experiments have used fetal or embryonic sources that may induce immunological rejection and generate ethical concerns. Autologous sources, in which the cells to be implanted are derived from recipients' own cells after reprogramming to stem cells, direct genetic modifications, or epigenetic modifications in culture, could eliminate many of these problems. In a previous study on autologous brain cell transplantation, we demonstrated that adult monkey brain cells, obtained from cortical biopsies and kept in culture for 7 weeks, exhibited potential as a method of brain repair after low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused dopaminergic cell death. The present study exposed monkeys to higher MPTP doses to produce significant parkinsonism and behavioral impairments. Cerebral cortical cells were biopsied from the animals, held in culture for 7 weeks to create an autologous neural cell "ecosystem" and reimplanted bilaterally into the striatum of the same six donor monkeys. These cells expressed neuroectodermal and progenitor markers such as nestin, doublecortin, GFAP, neurofilament, and vimentin. Five to six months after reimplantation, histological analysis with the dye PKH67 and unbiased stereology showed that reimplanted cells survived, migrated bilaterally throughout the striatum, and seemed to exert a neurorestorative effect. More tyrosine hydroxylase-immunoreactive neurons and significant behavioral improvement followed reimplantation of cultured autologous neural cells as a result of unknown trophic factors released by the grafts.

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Autologous Adult Cortical Cell Transplantation Enhances Functional Recovery Following Unilateral Lesion of Motor Cortex in Primates: A Pilot Study

Abstract: These pilot data, derived from 2 monkeys treated differently, suggest that, in the present experimental conditions, autologous adult brain progenitor cell transplantation in a nonhuman primate is safe and promotes enhancement of functional recovery.

Cited by 35 publications

References 39 publications

Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: Evidence for a contribution of the dorsolateral prefrontal cortex

Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: Evidence for a contribution of the dorsolateral prefrontal cortex

Distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects

Primate adult brain cell autotransplantation produces behavioral and biological recovery in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced parkinsonian St. Kitts monkeys

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