Ceftriaxone and the Nervous System

[LymeEnigma]

Abstract: Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression.

Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB.

Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA. jrothste@jhmi.edu

Glutamate is the principal excitatory neurotransmitter in the nervous system. Inactivation of synaptic glutamate is handled by the glutamate transporter GLT1 (also known as EAAT2; refs 1, 2), the physiologically dominant astroglial protein. In spite of its critical importance in normal and abnormal synaptic activity, no practical pharmaceutical can positively modulate this protein. Animal studies show that the protein is important for normal excitatory synaptic transmission, while its dysfunction is implicated in acute and chronic neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, brain tumours and epilepsy. Using a blinded screen of 1,040 FDA-approved drugs and nutritionals, we discovered that many beta-lactam antibiotics are potent stimulators of GLT1 expression. Furthermore, this action appears to be mediated through increased transcription of the GLT1 gene. beta-Lactams and various semi-synthetic derivatives are potent antibiotics that act to inhibit bacterial synthetic pathways. When delivered to animals, the beta-lactam ceftriaxone increased both brain expression of GLT1 and its biochemical and functional activity. Glutamate transporters are important in preventing glutamate neurotoxicity. Ceftriaxone was neuroprotective in vitro when used in models of ischaemic injury and motor neuron degeneration, both based in part on glutamate toxicity. When used in an animal model of the fatal disease ALS, the drug delayed loss of neurons and muscle strength, and increased mouse survival. Thus these studies provide a class of potential neurotherapeutics that act to modulate the expression of glutamate neurotransmitter transporters via gene activation.

PMID: 15635412 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

From What's Old is New Again - Antibiotic Protects Nerves By Removing Excess Glutamate:

The potentially therapeutic properties of ceftriaxone for ALS have little to do with its antibiotic effects but instead result from its ability to increase the number of glutamate transporters. Glutamate transporters are proteins that vacuum up the excitatory neurotransmitter glutamate. Normally, glutamate acts to excite nerves so that electrical signals can travel from one to the next. Too much glutamate has a toxic effect on nerve cells and has been implicated in neurodegenerative diseases such as ALS, Huntington's disease, Alzheimer's disease, epilepsy and stroke. Removing glutamate through the transporter prevents nerve damage caused by excessive amounts of glutamate.

http://www.ninds.nih.gov/news_and_event ... iaxone.htm

Another long shot, here, but could it be that, for some people suffering from chronic neuro Lyme, whether or not continued infection is going on is moot; perhaps it's the other properties to some of these antibiotics, and not simply the antimicrobial properties, that are keeping some Lyme patients out of wheelchairs?

[Nick]

Another long shot, here, but could it be that, for some people suffering from chronic neuro Lyme, whether or not continued infection is going on is moot; perhaps it's the other properties to some of these antibiotics, and not simply the antimicrobial properties, that are keeping some Lyme patients out of wheelchairs?

there are many other problems in chronic lyme than just these problems that are related to glutamate metabolism. But it is clear that many antibiotics have other effects than just the anti-biotic properties, e.g. many seem to have an anti-inflammatory effect that may reduce symptoms like pain as long as the antibiotic is used. In that sense some antibiotics are just (temporary) reducing the symptoms and not curing the disease.

Other than that, I am pretty sure that for people with severe neurologic problems the anti-biotic properties are the most important ones. You will often see than people who could no longer walk can walk again after just a few weeks on ceftriaxone. When the ceftriaxon is no longer administered, some symptoms will return but usually the severe paralyses etc. is gone for a long time or even for good (according to anecdotical evidence, I don't have official research to back it up).