Central nervous system trans-synaptic effects of acute axonal injury: a 1H magnetic resonance spectroscopy study.
N-acetylaspartate (NAA) has previously been proposed as a neuronal marker. 1H magnetic resonance spectroscopy (MRS) is able to detect NAA in brain, and decreases of NAA have been documented after brain injury. The reason for this decrease is not fully understood and neuron loss damage and "dysfunction" have all been proposed. It is hypothesized that acute central nervous system (CNS) deafferentation causes a trans-synaptic NAA decrease and that high resolution 1H MRS is able to detect such a decrease. To test this hypothesis, an experimental model was used in which axonal lesions were obtained by stretch injury in guinea pig right optic nerve (95-99% crossed fibers). The trans-synaptic concentration of NAA, total creatine (Cr), and the NAA/Cr ratio in lateral geniculate bodies (LGB) and superior colliculi (SC) sample extracts were measured 72 h later by high resolution 1H MRS. In the left LGB/SC, which is where right optic nerve fibers project, reductions of NAA and NAA/Cr were found whereas Cr levels were normal. NAA, NAA/Cr, and Cr values were all normal in the right LGB/SC. Histology and EM findings revealed no abnormalities. At 7 days, left LGB/SC NAA and NAA/Cr values were in the normal range. It was concluded that 1) acute deafferentation in the CNS causes a trans-synaptic decrease of NAA levels that can be detected by 1H MRS and 2) NAA decrease may be due to changes of NAA metabolism caused by functional neuronal inactivity rather than neuronal loss, injury or "dysfunction." 1H MRS is a potential tool for the study of functional effect of CNS lesions in vivo.
Rango
M
M
Università degli Studi di Milano, Istituto di Clinica Neurologica, Italy.
Spagnoli
D
D
Tomei
G
G
Bamonti
F
F
Scarlato
G
G
Zetta
L
L
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000502:physiology; D003401:Creatine / Q000378:metabolism; D005260:Female; D005829:Geniculate Bodies / Q000378:metabolism* / Q000648:ultrastructure; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration; D009900:Optic Nerve / Q000378:metabolism / Q000502:physiology; D020221:Optic Nerve Injuries; D011522:Protons; D013477:Superior Colliculi / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine