Here it will be released into the synaptic cleft and allowed to bind with the presynaptic membrane of inhibitory neurons in a similar manner seen with the binding to the motor neuron. Internalization
Tetanus toxin is then internalized again via endocytosis, this time in an acidic vesicle. In a mechanism not well understood, depolarization caused by the firing of the inhibitory neuron causes the toxin to be pulled into the neuron inside vesicles. Membrane translocation
The toxin then needs a way to get out of the vesicle and into the neuron cytosol for it to act on its target. The low pH of the vesicle lumen causes a conformational change in the toxin, shifting it from a water-soluble form to a hydrophobic form. With the hydrophobic patches exposed, the toxin can slide into the vesicle membrane. The toxin forms an ion channel in the membrane that is nonspecific for Na+, K+, Ca2+, and Cl− ions. There is a consensus among experts that this new channel is involved in the translocation of the toxins light chain from the inside of the vesicle to the neuron cytosol, but the mechanism is not well understood or agreed upon. It has been proposed that the channel could allow the light chain (unfolded from the low pH environment) to leave through the toxin pore, or that the pore could alter the electrochemical gradient enough, by letting in or out ions, to cause osmotic lysis of the vesicle, spilling the vesicles contents. Enzymatic target cleavage
The light chain of the tetanus toxin is zinc-dependent protease.
Tracheotomy is recommended for securing the airway because the presence of an endotracheal tube is a stimulus for spasm
Magnesium sulfate, as an intravenous infusion, to control spasm and autonomic dysfunction
Diazepam as a continuous IV infusion
The autonomic effects of tetanus can be difficult to manage (alternating hyper- and hypotension hyperpyrexia/hypothermia) and may require IV labetalol, magnesium, clonidine, or nifedipineDrugs such as diazepam or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to paralyze the person with curare-like drugs and use a mechanical ventilator.To survive a tetanus infection, the maintenance of an airway and proper nutrition are required. An intake of 3,500 to 4,000 calories and at least 150 g of protein per day is often given in liquid form through a tube directly into the stomach (percutaneous endoscopic gastrostomy), or through a drip into a vein (parenteral nutrition). This high-caloric diet maintenance is required because of the increased metabolic strain brought on by the increased muscle activity. Full recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminals.The antibiotic of choice is metronidazole. It can be given as intravenously, by mouth, or by rectum. Of likewise efficiency is penicillin, but some raise the concern of provoking spasms because it inhibits GABA receptor, which is already affected by tetanospasmin. Epidemiology
In 2013 it caused about 59,000 deaths – down from 356,000 in 1990.