By M. Gorok. University of Minnesota-Crookston.
Thus the disorder could be due to: NEUROTRANSMITTER FUNCTION IN HUMANS 297 (1) An actual degeneration of a NTpathway or (2) No actual degeneration but a biochemical abnormality or some circuitry failure order shuddha guggulu 60caps on line, leading to inadequate or excessive activity of the NT. The requirement in respect of NT function may be: (a) That it must be released physiologically from its nerve terminals by appropriate synaptic activity in order to produce the desired effect or (b) That it is sufficient merely to provide the NT at the synapse, without the need for it to be released physiologically. Clearly a disorder combining (1) with (a) would mean that little improvement could be expected by manipulating the lost NT, since the nerves are no longer there to release it physiologically. The main hope then would be to try to replenish the neurons with transplants (regeneration may be possible one day) and hope they become appro- priately innervated, or modify the action of some other NTwhich has become exaggerated (or reduced), as a result of the primary NTloss. By contrast it is easier to treat a disorder, whether characterised by neuronal degeneration ((1) above) or not (2), if it is sufficient just to provide NT(b), as appears to be the case in Parkinsonism. Of course, the effectiveness and specificity of any of the above manipulations will depend on how widely the NTis distributed and used and whether the malfunction applies only to one area or activity. Thus trying to increase (or decrease) the activity of a NTin only one area will be difficult if it has actions elsewhere which have not been affected by the disorder. The nervous system also has remarkable adaptive powers so the synaptic loss (or increase) of a NTis generally followed by a local compensating increase (decrease) in postsynaptic receptor number. This can be a useful response initially but it will be negated by the therapeutic provision of more (less) NT. Also a change in the activity of one NTcan lead to desirable compensating changes in the function of other NTs either working in conjunction with it or normally controlled by it. It must also be remembered that some NTs, like ACh, NA and 5-HT, have important peripheral as well as central roles and any attempt to modify them centrally will affect those peripheral effects as well. Thus if attempts made to increase the central action of a NT result in peripheral effects, these may be counteracted by using an appropriate antagonist that does not cross the blood±brain barrier.
For movement to tract buy cheap shuddha guggulu 60caps on line, whose axons descend in the medial spinal cord white occur, the initial posture must be altered by flexing some matter. These axons carry excitatory action potentials to body parts against gravity. Balance must be maintained dur- interneurons that influence alpha and gamma motor neuron ing movement, which is achieved by postural reflexes initi- pools of axial muscles. The medullary area gives rise to the ated by several key sensory systems. Vision, the vestibular medullary reticulospinal tract, whose axons descend system, and the somatosensory system are important for mostly ipsilateral in the anterior spinal white matter. A neu- presence is associated with lesions of the mesencephalon rological examination performed about 30 minutes after that isolate the portions of the brainstem below that level onset of the collapse shows no response to verbal stim- from the influence of higher centers. No spontaneous movements of the limbs are ob- ture is a result of extreme activation of the antigravity ex- servable. A mildly painful stimulus, compression of the tensor muscles by the unopposed action of the lateral soft tissue of the supraorbital ridge, causes immediate vestibular nucleus and the vestibulospinal tract. This pos- of this condition can be produced in experimental animals ture relaxes within a few seconds after the stimulation by a surgical lesion located between the mesencephalon is stopped. It can also be shown in experimental animals undergoes a magnetic resonance imaging (MRI) study that a destructive lesion of the lateral vestibular nucleus re- of the brain. The study demonstrates a large area of lieves the rigidity on that side. An area is said to have a mo- tract tor function if Rubrospinal Reticulospinal tract tract • Stimulation using very low current strengths elicits Medullary movements. Pontine Cervical • Destruction of the area results in a loss of motor func- tion.
They probably reflect the consequences of intense neuronal activation since in patients dying in status epilepticus they appear to be of recent origin and can be induced in animals by systemic or locally administered convulsant (see Meldrum and Corsellis 1984) buy 60 caps shuddha guggulu. Everyone is capable of having a convulsion, indeed their induction has been a common treatment for depression. The convulsive threshold of an epileptic, or more precisely that of some of their neurons, is just lower than normal. There is no known genetic basis for most of the common epilepsies apart from juvenile myoclonic epilepsy and childhood absence epilepsy which are dependent on inheritance of two or more susceptible genes, although genetic factors might more generally determine predisposition. Single distinct mutant genes have been established, however, in three rare forms of epilepsy (less than 1% of total), namely generalised epilepsy with febrile seizures, benign familial neonatal convulsions and autosomal dominant epilepsy (see McNamara 1999). These each encode a part of some voltage- gated ion channel which are believed to be respectively the b subunit of a Na channel (SCNIB), novel K channels and the a subunit of cholinergic nicotinic receptors (CHRNA4). All could lead to increased neuronal excitability and in fact co-expression in oocytes of the Na channel a subunit with the b subunit found in febrile convulsions produces a channel that inactivates more slowly than when it is expressed with normal b subunits. DEVELOPMENT OF AN EPILEPTIC SEIZURE A seizure is accompanied by a burst of spikes in the EEG. Between these so-called ictal phases are solitary EEG interictal spikes. Each of them represents the field potential associated with a burst of action potentials in a group of neurons within the epileptic focus (Fig. Focal neurons when activated show an abnormal excitatory postsynaptic potential (EPSP) called the paroxysmal depolarising shift (PDS) (Fig. While such neurons can be found anywhere they are more common in the CA3 region of the hippocampus and layer 4 of the cerebral cortex. Neurons showing this burst firing are also called Group I, pacemaker or epileptic neurons and their activation always results in a burst discharge and not a single impulse. Thus they could have a persisting abnormality in membrane or ion channel excitability.