Rodrigo Ramos-Zúñiga

Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine

Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer.

Trans-supraorbital approach to supratentorial aneurysms.

OBJECTIVE The trans-supraorbital approach has the advantage of combining the keyhole principle with cranial base surgery. The anatomic fields that can be visualized with the use of this procedure have been demonstrated in cadavers, and the advantages and potential surgical applications of this procedure are described in this report. This article is the first to describe a group of intracranial supratentorial aneurysms. METHODS We used the trans-supraorbital approach in 22 cases of supratentorial aneurysms. In this technique, an incision is made through the eyebrow, then a 3.5-cm craniotomy is performed with en bloc extension to the orbital arch, complemented by different drilling extensions of the orbital roof according to the surgical objective. We describe the anatomic details of the experimental work as well as the clinical results. RESULTS The trans-supraorbital technique offers an unlimited wide exposure of neurovascular structures in this microsurgical corridor. The craniotomy extension allows greater exposure than the conventional keyhole supraorbital approach, which makes the technique safe for the patient and comfortable for the surgeon. All patient outcomes were successful; no serious complications from the surgical technique occurred. Our success was achieved through better microscopic illumination in the deep field and by gaining access to the complete supratentorial vascular territory with minimal cerebral retraction and an acceptable cosmetic result. CONCLUSION The trans-supraorbital approach is effective for gaining access to and treating supratentorial aneurysms. Also, the microsurgical field is more convenient in microscope-assisted surgery because total reliance on the endoscope is not required, and minimal brain retraction is needed. This modification of the keyhole procedure also provides multiple surgical options in this microsurgical corridor, using the principles of minimal invasiveness in cranial base surgery.

Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders

The psychiatric disorders are one of the most disabling illnesses in the world and represent a major problem for public health. These disorders are characterized by neuroanatomical or biochemical changes and it has been suggested that such changes may be due to inadequate neurodevelopment. Diverse alterations in the gene expression and/or serum level of specific growth factors have been implicated in the etiology, symptoms and progression of some psychiatric disorders. Herein, we summarize the latest information regarding the role of brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), fibroblast growth factor (FGF), Insulin-like growth factor (IGF-1), neuroregulin-1 (NGR-1), erythropoietin (EPO), vascular growth factor (VEGF), transforming growth factor beta (TGF-β), nerve growth factor (NGF) and others cytokines in the pathogenesis of schizophrenia, depression, bipolar and anxiety disorders. Focusing on the role of these growth factors and their relationship with the main impairments (cognitive, emotional and social) of these pathologies. Some of these signaling molecules may be suitable biological markers for diagnosis and prognosis in cognitive, mood and social disabilities across different mental disorders.

A New Bilayer Chitosan Scaffolding as a Dural Substitute: Experimental Evaluation

OBJECTIVE To evaluate whether bilayer chitosan scaffolding (BChS) can provide a watertight dural closure and permit regeneration by fibroblasts in an experimental in vivo model. METHODS In the in vitro phase, BChS was elaborated and the following characteristics were evaluated: pore size, thickness, water absorption capacity, tensile strength, strain, and toughness. In the second in vivo phase, 27 durectomized New Zealand rabbits were randomly assigned into three duraplasty groups with autologous dura, collagen matrix (CM), or BChS. In all groups, fluid leakage pressure was measured at 10, 21, or 180 days. Histology response to regeneration was evaluated through hematoxylin and eosin stain. RESULTS BChS was standardized to obtain bilayer scaffoldings with a nonporous layer and a porous layer. The pore size was 10 μm, total thickness was 400 μm, strain was 57.8%, and tensile strength was 5.5 gr/mm(2). The physical characteristics of BChS allowed dural closure without cerebrospinal fluid (CSF) leak. There were no differences in fluid leakage pressures between the BChS, dura, and CM groups. Histologic analysis showed fibroblast migration with adequate dural regeneration. CONCLUSIONS BChS is an ideal alternative for a watertight dural closure because it can be sutured, and it induces organized regeneration with fibroblasts without evidence of fibrosis.

Ethical Implications in the Use of Embryonic and Adult Neural Stem Cells

The advent and growth of technological advances have led to new routes of knowledge. Thereby, we currently face new challenges. We have just started to get a glimpse of the structural and functional role of neural stem cells in differentiation and migration processes, the origin of synaptic networks, and subsequent readjustments in specific circuits. A whole range of treatment possibilities originates from this knowledge that potentially can be used for different neurological diseases in humans. Although this is an encouraging scenario, it implies that the human brain is the object of such study, as well as its potential manipulation and transplantation. It is, therefore, pertinent that ethical principles should be followed in such research to have proper balance between what can be done and what should be done, according to every specific context. Hence, it is wise to consider ethical implications in every research project, along with potential clinical applications, under the principle of causing no harm, following risk and benefit rules in decision making and with respect of the human condition as a priority.

Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.

Sleep deprivation (SD) affects spatial memory and proliferation in the dentate gyrus. It is unknown whether these deleterious effects persist in the long run. The aim of this study was to evaluate the proliferation, differentiation and maturation of neural progenitors as well as spatial memory 21 days after suffering SD. Sixty-day old male Balb/C mice were exposed to 72-h REM-SD. Spatial memory, cell fate, apoptosis and expression levels of insulin-like growth factor 1 receptor (IGF-1R) were evaluated in the hippocampus at 0, 14, and 21 days after SD or control conditions. After 21-days recovery period, memory performance was assessed with the Barnes maze, we found a significant memory impairment in SD mice vs. control (94.0 ± 10.2 s vs. 25.2 ± 4.5 s; p < 0.001). The number of BrdU+ cells was significantly decreased in the SD groups at day 14 (controls = 1.6 ± 0.1 vs. SD mice = 1.2 ± 0.1 cells/field; p = 0.001) and at day 21 (controls = 0.2 ± 0.03 vs. SD mice = 0.1 ± 0.02 cells/field; p < 0.001). A statistically significant decrease was observed in neuronal differentiation (1.4 ± 0.1 cells/field vs. 0.9 ± 0.1 cells/field, p = 0.003). Apoptosis was significantly increased at day 14 after SD (0.53 ± 0.06 TUNEL+ cells/field) compared to controls (0.19 ± 0.03 TUNEL+ cells/field p < 0.001) and at 21-days after SD (SD mice 0.53 ± 0.15 TUNEL+ cells/field; p = 0.035). At day 0, IGF-1R expression showed a statistically significant reduction in SD animals (64.6 ± 12.2 units) when compared to the control group (102.0 ± 9.8 units; p = 0.043). However, no statistically significant differences were found at days 14 and 21 after SD. In conclusion, a single exposition to SD for 72-h can induce deleterious effects that persist for at least 3 weeks. These changes are characterized by spatial memory impairment, reduction in the number of hippocampal BrdU+ cells and persistent apoptosis rate. In contrast, changes IGF-1R expression appears to be a transient event. Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time.

Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice.

Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation.

Early-life exposure to noise reduces mPFC astrocyte numbers and T-maze alternation/discrimination task performance in adult male rats

In this experiment, we evaluated the long-term effects of noise by assessing both astrocyte changes in medial prefrontal cortex (mPFC) and mPFC-related alternation/discrimination tasks. Twenty-one-day-old male rats were exposed during a period of 15 days to a standardized rats′ audiogram-fitted adaptation of a human noisy environment. We measured serum corticosterone (CORT) levels at the end of the exposure and periodically registered body weight gain. In order to evaluate the long-term effects of this exposure, we assessed the rats′ performance on the T-maze apparatus 3 months later. Astrocyte numbers and proliferative changes in mPFC were also evaluated at this stage. We found that environmental noise (EN) exposure significantly increased serum CORT levels and negatively affected the body weight gain curve. Accordingly, enduring effects of noise were demonstrated on mPFC. The ability to solve alternation/discrimination tasks was reduced, as well as the number of astroglial cells. We also found reduced cytogenesis among the mPFC areas evaluated. Our results support the idea that early exposure to environmental stressors may have long-lasting consequences affecting complex cognitive processes. These results also suggest that glial changes may become an important element behind the cognitive and morphological alterations accompanying the PFC changes seen in some stress-related pathologies.

A microsurgical anterior cervical approach and the immediate impact of mechanical retractors: A case control study.

Introduction: A microsurgical anterior cervical approach with discectomy and fusion (MACDF) is one of the most widely used procedures for treating radicular disorders. This approach is highly successful; however, it is not free from complications. These can be associated with soft tissue injuries. Aim of the Study: The recognition of the risks for these complications should be identified for timely prevention and safe treatment. Materials and Methods: Study Design: Retrospective case control study. This study includes a retrospective case series of 37 patients, paying special attention to immediate complications related to the use of mechanical retraction of soft tissue (dysphagia, dysphonia, esophageal lesions and local hematoma); and a comparative analysis of the outcomes after changes in the retraction method. Results: All selected cases had a positive neurological symptom response in relation to neuropathic pain. Dysphagia and dysphonia were found during the first 72 h in 94.1% of the cases in which automatic mechanical retraction was used for more than one hour during the surgical procedure. A radical change was noted in the reduction of the symptoms after the use of only manual protective blades without automatic mechanical retraction: 5.1% dysphagia and 0% dysphonia in the immediate post-operative period, P = 0.001. Conclusions: Soft tissue damage due to the use of automatic retractors in MACDF is not minor and leads to general discomfort in the patient in spite of good neurological results. These problems most often occur when automatic retractors are used continuously for more than 1 hour, as well as when they are used in multiple levels. Dysphagia, dysphonia and local pain decreased with the use of transient manual blades for retraction, and with intermittent release following minimally invasive principles.

Postconcussion Syndrome and Mild Head Injury: The Role of Early Diagnosis Using Neuropsychological Tests and Functional Magnetic Resonance/Spectroscopy

OBJECTIVE Postconcussion syndrome (PCS) is usually underestimated in cases of mild head injury (MHI). It is one of the most common causes of physical, cognitive, and psychomotor disturbances that affect the quality of life, work, and social reintegration of individuals. Until now, we did not have evidence of structural abnormalities shown by traditional imaging methods. We describe a series of instruments that confirm PCS with satisfactory evidence. METHODS We conducted a clinical prospective study of 19 adult patients selected from a pool of 320 adults who had MHI. The cognitive, executive, and memory functions of subjects were examined within the first 72 hours using neuropsychological tests. These results were analyzed with neurological examination and functional MR/spectroscopy. RESULTS Neurobehavioral alterations were found in 47% of cases, with posttraumatic amnesia. Around 55% of subjects experienced physical disturbances such as headache and postural vertigo due to PCS. The spectroscopy reports revealed neurometabolite disturbances in 54% of cases, particularly N-acetylaspartate (Naa) and the Naa/lactate ratio in the frontal lobe. We observed a relationship between metabolite disturbances in spectroscopy and the digit span backward test (P = .045). CONCLUSIONS This first diagnostic strategy supports with scientific evidence the presence of PCS in MHI. We identified physical and neuropsychological abnormalities from this group, affecting the areas of memory and learning. Evidence of neurometabolite disturbances were found specifically in the frontal lobe. It is necessary to complete comparative follow-up for an extended period of time. The neuropsychological and spectroscopy tests allow us to confirm the diagnosis of a syndrome that is usually neglected.