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Targeting the Nervous System
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Nerves transmit signals between the CNS, made up of the brain and spinal cord, to the body (peripheral nervous system). The motor nerves of the peripheral nervous system are divided into three subsystems. The somatic motor nervous system carries signals from the CNS to skeletal muscle to stimulate voluntary muscle contraction. The autonomic nervous system carries messages from the CNS to smooth muscle, cardiac muscle, and the adrenal medulla to stimulate the release of adrenaline. These nervous impulses are divided across two pathways. Parasympathetic nerves leave the CNS, travel some distance before encountering a synapse with a second nerve, and then the nerve impulse is transmitted across the junction using the neurotransmitter acetylcholine. Sympathetic nerves leave the CNS, but almost immediately synapse with a second nerve, again using acetylcholine. The second nerve proceeds to the same target organs as the parasympathetic pathway, but the synapses also have different receptors, that use different neurotransmitter: noradrenaline. These two systems tend to have an antagonistic relationship, where the sympathetic nervous system gets the body ready for action, and the parasympathetic calms the body down.
Brainstem and Cardiovascular Regulation
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
Ching-Jiunn Tseng, Che-Se Tung
Central control of the cardiovascular system is complex and still not well understood. The central nervous system (CNS) receives sensory information from many sources and sends out appropriate regulatory signals to several effector organs. It has been suggested that disturbances of these regulatory mechanisms may be involved in chronic elevation in systemic arterial pressure (Reis, 1981). For instance, abnormalities in central autonomic control may occur early in the course of borderline hypertension, and then over a period of years, through a sequence of secondary changes, lead to essential hypertension (Reis, 1981). Whether central autonomic control plays a role in borderline or essential hypertension is still unknown. Indeed, the neuronal circuitry in the brain is so complex that we still do not know the precise mechanisms of the depressor effect of some of the most commonly employed antihypertensive drugs, such as α-methyldopa and clonidine. But the more we understand about central cardiovascular regulatory mechanisms, the more we can assess its role in cardiovascular disease, and the more rationally we can approach new drug development. The aim of this chapter is to introduce key features of the brainstem neural cardiovascular control system.
Antiepileptic Drug Toxicity: An Overview
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
The nervous system is usually subdivided into the central nervous system and peripheral system. For the purposes of this discussion, the central nervous system will be broadly subdivided into functional systems consisting of the reticular activating system (sedation and sleep), cortex (cognitive), the limbic system (emotional), cerebellar system (balance), and the extrapyramidal (movement disorders). While it is not always possible to clearly separate toxicity in one system from the others, somewhat specific patterns involving these systems have been observed for the various antiepileptic drugs (Table 1).
A non-invasive direct nose to brain drug delivery platform vs. invasive brain delivery approach: patient-centered care impact analysis
Published in Drug Delivery, 2022
Ayala Kobo-Greenhut, Hilel Frankenthal, Aziz Darawsha, Avraham Karasik, Adit Zohar Beja, Tamir Ben Hur, Dana Ekstein, Lisa Amir, Daniel Shahaf, Izhar Ben Shlomo, Iris Shichor, William H. Frey
Herein we report on PCIA’s implementation via a comparative assessment of SipNose, a novel noninvasive Direct Nose-to-Brain (DNTB) delivery platform that delivers drugs to the central nervous system (CNS), versus intrathecal and intracerebroventricular injection (Invasive I/I) as the standard-of-care invasive technology for CNS drug delivery. Both latter methods are well-known, widely used, invasive treatment modalities for the management of central nervous system (CNS) disorders. These well-established modes of invasive drug delivery assume that effective delivery of therapeutics to the brain can only be achieved via a platform that invasively crosses the blood-brain-barrier (BBB). This is deemed necessary either due to most drugs’ inability to penetrate the BBB, or in the case of BBB penetrating drugs (less than 2% of existing drugs), due to these methods’ allowing for low dose of drug to be delivered near the site of action. This direct delivery to the target site reduces drug adverse effects and their severity (Delhaas & Huygen, 2020). Conversely, the noninvasive DNTB technology takes advantage of the physiological structure of the nasal cavity and its proximity to the olfactory and trigeminal nerve pathways, to allow for efficient direct drug absorption and delivery from the upper nasal cavity to the CNS along these neuronal pathways, thereby bypassing the BBB (Chen et al., 1998; Dhuria et al., 2010; Gomez et al., 2012). Direct nose to brain drug transport allows for an enormous range of neurotherapeutic molecular sizes to be delivered noninvasively to the CNS (Chapman et al., 2013; Kosyakovsky et al., 2021).
The impact of coronavirus 2019 (COVID-19) on neurosurgical practice and training: a review article
Published in British Journal of Neurosurgery, 2022
Ehsan Alimohammadi, Sonia V. Eden, Sharath Kumar Anand, Paniz Ahadi, Arash Bostani, Seyed Reza Bagheri
Mao et al. in a retrospective study evaluated neurological manifestations of COVID-19 in 214 affected patients. They categorized neurological symptoms into three categories including, central nervous system (CNS) symptoms such as headache, impaired consciousness, dizziness, ataxia, stroke, and epilepsy, peripheral nervous system (PNS) symptoms such as hypopsia, hypogeusia, hyposmia, neuralgia, and skeletal muscle injury such as skeletal muscle pain and elevated serum creatine kinase. These symptoms are summarized in Table 1. Their results showed that 78 (36.4%) patients had neurological manifestations and neurological symptoms were associated with more severe respiratory disease. They reported an incidence of 5.7%, 14.8%, and 19.3% for acute cerebrovascular diseases, impaired consciousness, and skeletal muscle injury, respectively, in patients with severe disease according to their respiratory status compared to an incidence of about 0.8%, 2.4%, and 4.8% in those with non-severe disease.9
Effects of tandem walk and cognitive and motor dual- tasks on gait speed in individuals with chronic idiopathic neck pain: a preliminary study
Published in Physiotherapy Theory and Practice, 2021
Munlika Sremakaew, Somporn Sungkarat, Julia Treleaven, Sureeporn Uthaikhup
The importance of cervical afferent input to the postural control system is well documented (Bove, Diverio, Pozzo, and Schieppati, 2001; Courtine, Papaxanthis, Laroche, and Pozzo, 2003; Vuillerme and Pinsault, 2009). Sensory information from the cervical spine is relayed into the central nervous system, where it is integrated with other sensory information from visual, vestibular, and somatosensory systems (Kristjansson and Treleaven, 2009; Treleaven, 2008). Altered cervical afferent input to the central nervous system can cause impaired postural orientation and equilibrium. Numerous studies demonstrated that patients with chronic neck pain had increased postural sway during quiet standing in different conditions (Field, Treleaven, and Jull, 2008; Juul-Kristensen et al., 2013; Treleaven, Jull, and Lowchoy, 2005). Additionally, they had difficulty balancing in walking, particularly with challenging conditions such as with head movements and at the maximum speed (Poole, Treleaven, and Jull, 2008; Sjostrom et al., 2003; Uthaikhup et al., 2014). Such changes in postural stability may be associated with an increased risk of falls (Ambrose, Paul, and Hausdorff, 2013).