Aleksandar Jankovski

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low βIII tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals.

Intraoperative magnetic resonance imaging at 3-T using a dual independent operating room-magnetic resonance imaging suite: development, feasibility, safety, and preliminary experience.

OBJECTIVEA twin neurosurgical magnetic resonance imaging (MRI) suite with 3-T intraoperative MRI (iMRI) was developed to be available to neurosurgeons for iMRI and for independent use by radiologists. METHODSThe suite was designed with one area dedicated to neurosurgery and the other to performing MRI under surgical conditions (sterility and anesthesia). The operating table is motorized, enabling transfer of the patient into the MRI system. These two areas can function independently, allowing the MRI area to be used for nonsurgical cases. We report the findings from the first 21 patients to undergo scheduled neurosurgery with iMRI in this suite (average age, 51 ± 24 yr; intracranial tumor, 18 patients; epilepsy surgery, 3 patients). RESULTSTwenty-six iMRI examinations were performed, 3 immediately before surgical incision, 9 during surgery (operative field partially closed), and 14 immediately postsurgery (operative field fully closed but patient still anesthetized and draped). Minor technical dysfunctions prolonged 10 iMRI procedures; however, no serious iMRI-related incidents occurred. Twenty-three iMRI examinations took an average of 78 ± 20 minutes to perform. In three patients, iMRI led to further tumor resection because removable residual tumor was identified. Complete tumor resection was achieved in 15 of the 18 cases. CONCLUSIONThe layout of the new complex allows open access to the 3-T iMRI system except when it is in use under surgical conditions. Three patients benefited from the iMRI examination to achieve total resection. No permanent complications were observed. Therefore, the 3-T iMRI is feasible and appears to be a safe tool for intraoperative surgical planning and assessment.

Reliable EEG responses to the selective activation of C-fibre afferents using a temperature-controlled infrared laser stimulator in conjunction with an adaptive staircase algorithm.

Summary C‐fibre laser‐evoked potentials can be obtained reliably at single‐subject level from the hand and foot using a temperature‐controlled CO2 laser combined with an adaptive algorithm based on reaction times. ABSTRACT Brain responses to the activation of C‐fibres are obtained only if the co‐activation of A&dgr;‐fibres is avoided. Methods to activate C‐fibres selectively have been proposed, but are unreliable or difficult to implement. Here, we propose an approach combining a new laser stimulator to generate constant‐temperature heat pulses with an adaptive paradigm to maintain stimulus temperature above the threshold of C‐fibres but below that of A&dgr;‐fibres, and examine whether this approach can be used to record reliable C‐fibre laser‐evoked brain potentials. Brief CO2 laser stimuli were delivered to the hand and foot dorsum of 10 healthy subjects. The stimuli were generated using a closed‐loop control of laser power by an online monitoring of target skin temperature. The adaptive algorithm, using reaction times to distinguish between late detections indicating selective activation of unmyelinated C‐fibres and early detections indicating co‐activation of myelinated A&dgr;‐fibres, allowed increasing the likelihood of selectively activating C‐fibres. Reliable individual‐level electroencephalogram (EEG) responses were identified, both in the time domain (hand: N2: 704 ± 179 ms, P2: 984 ± 149 ms; foot: N2: 1314 ± 171 ms, P2: 1716 ± 171 ms) and the time‐frequency (TF) domain. Using a control dataset in which no stimuli were delivered, a Receiver Operating Characteristics analysis showed that the magnitude of the phase‐locked EEG response corresponding to the N2‐P2, objectively quantified in the TF domain, discriminated between absence vs presence of C‐fibre responses with a high sensitivity (hand: 85%, foot: 80%) and specificity (hand: 90%, foot: 75%). This approach could thus be particularly useful for the diagnostic workup of small‐fibre neuropathies and neuropathic pain.

Intraoperative 3T MR Imaging for Spinal Cord Tumor Resection: Feasibility, Timing, and Image Quality Using a "Twin" MR-Operating Room Suite

SUMMARY: We assessed feasibility, safety, and timing of an original intraoperative MR procedure in 3 cases of resection of spinal cord glioma by using a clinical 3T MR system connected to an adjacent operating room in a design being coined “twin” or “dual” MR–operating room suite.

Anodal Transcutaneous Spinal Direct Current Stimulation (tsDCS) Selectively Inhibits the Synaptic Efficacy of Nociceptive Transmission at Spinal Cord Level

Recently studies have aimed at developing transcutaneous spinal direct current stimulation (tsDCS) as a non-invasive technique to modulate spinal function in humans. Independent studies evaluating its after-effects on nociceptive or non-nociceptive somatosensory responses have reported comparable effects suggesting that tsDCS impairs axonal conduction of both the spino-thalamic and the medial lemniscus tracts. The present study aimed to better understand how tsDCS affects, in humans, the spinal transmission of nociceptive and non-nociceptive somatosensory inputs. We compared the after-effects of anodal low-thoracic, anodal cervical and sham tsDCS on the perception and brain responses elicited by laser stimuli selectively activating Aδ-thermonociceptors of the spinothalamic system and vibrotactile stimuli selectively activating low-threshold Aβ-mechanoreceptors of the lemniscal system, delivered to the hands and feet. Low-thoracic tsDCS selectively and significantly affected the LEP-N2 wave elicited by nociceptive stimulation of the lower limbs, without affecting the LEP-N2 wave elicited by nociceptive stimulation of the upper limbs, and without affecting the SEP-N2 wave elicited by vibrotactile stimulation of either limb. This selective and segmental effect indicates that the neuromodulatory after-effects of tsDCS cannot be explained by anodal blockade of axonal conduction and, instead, are most probably due to a segmental effect on the synaptic efficacy of the local processing and/or transmission of nociceptive inputs in the dorsal horn.

Post-resection treatment of glioblastoma with an injectable nanomedicine-loaded photopolymerizable hydrogel induces long-term survival

ABSTRACT Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite available therapeutic options, the prognosis for patients with GBM remains very poor. We hypothesized that the intra‐operative injection of a photopolymerizable hydrogel into the tumor resection cavity could sustain the release of the anti‐cancer drug paclitaxel (PTX) encapsulated in poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles and prevent GBM recurrence. The tumor was resected 13days after implantation and a pre‐gel solution composed of polyethylene glycol dimethacrylate (PEG‐DMA) polymer, a photoinitiator and PTX‐loaded PLGA nanoparticles (PTX PLGA‐NPs) was injected into the tumor resection cavity. A solid gel filling the whole cavity was formed immediately by photopolymerization using a 400nm light. PTX in vitro release study showed a burst release (11%) in the first 8h and a sustained release of 29% over a week. In vitro, U87 MG cells were sensitive to PTX PLGA‐NPs with IC50 level of approximately 0.010&mgr;g/mL. The hydrogel was well‐tolerated when implanted in the brain of healthy mice for 2 and 4months. Administration of PTX PLGA‐NPs‐loaded hydrogel into the resection cavity of GBM orthotopic model lead to more than 50% long‐term survival mice (150days) compared to the control groups (mean survival time 52days). This significant delay of recurrence is very promising for the post‐resection treatment of GBM.