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Polyanhydride Microspheres As Drug Delivery Systems
Published in Max Donbrow, Microcapsules and Nanoparticles in Medicine and Pharmacy, 2020
Edith Mathiowitz, Robert Langer
Pharmacological treatment aimed at increasing critical acetylcholine activity in patients with Alzheimer’s disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to an adequate amount of drug. Using polyanhydride microspheres, a new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using microspheres made by solvent removal and containing bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run an eight-arm radial maze, after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 d. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similar, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however, displayed significant improvement within 10 d after implantation: this improvement persisted for the duration of the experiment (p <0.05, student’s t-test).
Basics of Human Biology
Published in Masanori Shukuya, Bio-Climatology for Built Environment, 2019
The second sub-structure consists of thalamus, hypothalamus, fornix, amygdala, hippocampus, and others. This is equivalent to the brain developed in the evolutional course from reptiles to lower mammals. It is called all together limbic system. The The thermoregulatory system is embedded within the hypothalamus, whose purpose is to keep the thermal homeostasis making use of the sensory information of warmth and coldness; this must have emerged with the development of small mammals and birds almost 250 million years ago, up until which there seems to have been quite a large fluctuation of environmental temperature as shown in Fig. 3.4. The emergence of thermoregulatory system may be considered to be the origin of space heating and cooling systems.
The Arbitrary Mapping of Sensory Inputs to Voluntary and Involuntary Movement: Learning-Dependent Activity in the Motor Cortex and Other Telencephalic Networks
Published in Alexa Riehle, Eilon Vaadia, Motor Cortex in Voluntary Movements, 2004
Peter J. Brasted, Steven P. Wise
In addition to lesions of the dorsal PM and the ventral and orbital PF, which substantially impair arbitrary sensorimotor mapping in terms of both acquisition and performance, disruption of the hippocampal system (HS) also impairs this behav- ior.86-88 However, lesioned monkeys can perform mappings learned preoperatively. This finding supports the idea that HS functions to store mappings in the intermediate term, as opposed to the short term (seconds) or the long term (weeks or months). The general idea89 is that repeated exposure to these associations results in consolidation of the mappings in neocortical networks.9 Impairments in learning new arbitrary visuomotor mappings result from fornix transection, the main input and output pathway for the HS, even when both the stimuli and responses are nonspatially differentiated.88 In contrast, monkeys with excitotoxic hippocampal lesions are not impaired in learning these "nonspatial" visuomotor mappings.90 This finding implies that the impairment on this nonspatial task seen after fornix transection reflects either the disruption of cholinergic inputs to areas near the hippocampus, such as the entorhinal cortex, or dysfunction within those areas due to other causes.
Finite element simulation of head impacts in mixed martial arts
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2021
Stephen Tiernan, Aidan Meagher, David O’Sullivan, Eoin O’Kelly
Simulation studies play a unique role in head impact investigations as they enable the determination of brain tissue stress and strain resulting from trauma. The Wayne state head model is one of the most detailed head models and is capable of simulating impacts up to 200 g and 12 krad/s2 (Zhang et al. 2001). This model was used to investigate concussion and determined that the largest strains occurred in the fornix, mid-brain and corpus callosum and that there was a significant correlation between strain and concussive symptoms (Viano, Casson, Pellman, Zhang, et al. 2005). Kleiven found lateral angular accelerations (in the coronal plane) gave rise to higher strains than impacts from other directions (Kleiven 2005). Generally, kinematic data are used to define the boundary conditions for simulation models. In order to quantify the kinematics of head impacts in US football Newman et al. recreated 27 impacts in a laboratory (Newman et al. 2000). Several researchers have used these data with simulation models to find the average strain in various brain regions of concussed players or the strain that related to a 50% probability of concussion. A 50% probability of concussion in US football has been reported for strains in the corpus callosum of 0.13 (Giordano and Kleiven 2014) to 0.21 (Kleiven 2007). The average strain in the corpus callosum of concussed Australian rules football and rugby players was 0.31 (Patton et al. 2013; McIntosh et al. 2014). High strains in the corpus callosum are thought to be due to lateral distortions of the falx, caused by high coronal angular accelerations (Ho et al. 2017).
Investigation of dynamic deformation of the midbrain in rear-end collision using human brain FE model
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2020
Noritoshi Atsumi, Masami Iwamoto, Yuko Nakahira, Yoshitaka Asano, Jun Shinoda
In this study, we used our previously developed human brain FE model (Atsumi et al. 2018). Figure 1 shows an overview of this model. The model geometry was based on commercially available 3 D data (Human Brain Ultimate, TurboSquid, USA) and CT/MRI data obtained from the Visible Human Project (NIH, USA). This model includes the cerebrum, cerebellum, falx, dura mater, pia mater, arachnoid, cerebrospinal fluid (CSF), ventricle, tentorium, and brain stem (which is subdivided into the midbrain, pons, and medulla, followed by the spinal cord) (Figure 1). In particular, this model sufficiently describes anatomical structures of the deep brain, such as the corpus callosum, thalamus, basal ganglia, and fornix. Most of these regions are composed of hexahedral solid elements, while the ventricle was modeled such that tetrahedral solid elements filled the continuous space around the deep brain. The mesh quality of the model was examined by four parameters such as Jacobian, aspect ratio, equiangle skew, and warpage (M&T Support 2017; Altair Hyperworks 2015, 2017). 91.9% of elements in the brain had a Jacobian above 0.70 (the minimum value was 0.30), 99.7% elements had an aspect ratio below 5.0 (the maximum value was 6.6), 74.4% of elements had an equiangle skew below 0.40 (the maximum value was 0.92), and 83.3% of elements had a warpage below 15 deg (the maximum value was 60.8 deg). Therefore, the mesh in our brain FE model has sufficient quality to predict brain injury.
The future potential of the Stentrode
Published in Expert Review of Medical Devices, 2019
Sam E. John, David B. Grayden, Takufumi Yanagisawa
The StentrodeTM was also used to stimulate the motor cortex to generate gross movements [2]. Neuromodulation or stimulation of the brain has offered life-changing treatments for people with neurological conditions such as Parkinson’s disease and epilepsy, usually by deep-brain stimulation. Using the venous approach, the StentrodeTM can reach prefrontal brain regions, motor and somatosensory regions, and parietal regions adjacent to the interhemispheric fissure [1,10]. Although more challenging, an intravascular device like the StentrodeTM may potentially reach the thalamus, fornix, nucleus accumbens, subgenual cingulate white matter, and ventral capsule [11]. However, the device will need to be made substantially smaller to access these regions with smaller blood vessels. At present, the StentrodeTM has not been able to show reliable stimulation since approximately 60% of experiments were successful in generating a motor response when stimulating in the region of the motor cortex of sheep [2]. An important first step to showing neuromodulation of the brain would be to generate consistent cortical responses. Initial evidence is positive and future work should be able to ascertain the limits of endovascular stimulation and its effect on the vasculature.