Biomedical subjects

Giorgio Brunelli

Publications and source records attributed to Giorgio Brunelli.

6 recordsLinked to original sources

PubMed2006

Glutamatergic innervation of rat skeletal muscle by supraspinal neurons: a new paradigm in spinal cord injury repair.

Acetylcholine is the specific chemical code of spinal nerve terminal transmission at the mammalian neuromuscular junction (NMJ), whereas nicotinic acetylcholine receptors inserted into the membrane of muscle fibres mediate signalling for the muscle response. Glutamate has a primary role in neuromuscular transmission of organisms that are phylogenetically distant from mammals, the invertebrates, including insect and molluscs. Recent research has shown that diverting descending glutamatergic fibres in the spinal cord to rat skeletal muscle by means of a peripheral nerve graft causes the cholinergic synapse to switch to the glutamatergic type. These data demonstrate that under appropriate surgical manipulation supraspinal neurons can directly target muscle fibres and specify the postsynaptic receptors to achieve a functional glutamatergic NMJ.

Animals↗

PubMed2006

Orbital fractures: a new classification and staging of 190 patients.

The orbit is located in the middle third of the face, composed of several bones and surrounded by complex anatomic structures so that orbital fractures (OF) often involve other parts of the face. A staging system for classifying OF is of paramount importance in order to exchange information between trauma centers. Several classifications have been proposed for describing OF but they have not a single method applicable to the whole orbit. Here, a classification for OF that can be summarized with four abbreviations is proposed. Four letters define the localization (F = frontal, N = nasal, M = maxillary and Z = zygomatic bone fracture), two acronyms describe fragment shift (in = blow-in or out = blow-out), four numbers define ocular movement impairment (1 = superior, 2 = internal, 3 = inferior, and 4 = external extrinsic muscular deficit) and two acronyms describe eye position (EX = exophthalmos and ENO = enophthalmos). To evaluate the suitability of the proposed classification a retrospective study on a series of 190 OFs is performed. Age, gender, new stage, clinical diagnosis at admission, type of surgery, and need for graft for orbital reconstruction are considered. A good correlation between the proposed classification and the studied variables is detected. In conclusion, the proposed classification is a simply and precise method to stage OF. It can summarize OF and be used in the daily practice. However, it is our belief that a multi-center study should be performed before the effectiveness of the proposed classification can be clearly stated.

Adolescent↗

PubMed2005

Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle.

Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connecting skeletal muscle to the lateral white matter of the spinal cord by grafting the distal stump of the transected motor nerve produced functional muscle reinnervation. The restored neuromuscular activity became resistant to common curare blockers but sensitive to the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Analysis of the regenerated nerve disclosed new glutamatergic axons and the disappearance of cholinergic fibers. Many axons belonged to the supraspinal neurons located in the red nucleus and the brainstem nuclei. Finally, the innervated muscle displayed high expression and clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits glutamate receptors 1 and 2. Our data suggest that supraspinal neurons can target skeletal muscle, which retains the plasticity to generate functional glutamatergic NMJ.

Action Potentials↗

PubMed2005

Research on the possibility of overcoming traumatic paraplegia and its first clinical results.

The interruption of the continuity of the spinal cord is still an incurable lesion. In contrast with the peripheral nerves, the axons regenerating from the mother cells of the brain do not progress inside the cord. The reasons of this "non-permissiveness" are still unclear. This article describes the attempts of the author to overcome this non-permissiveness by means of a research that began in 1980 on rats, and continued since 1993 on monkeys. Results of the research on experimental animals were good and convincing so that this operation has been performed on fully informed human being volunteers affected by total severance of the cord between T8 and T11. Results of the first clinical cases are presented regarding operations performed either by rerouting the ulnar nerve to the lower limbs, or connecting the rostral stump of the severed cord with peripheral nerves of the hip to obtain rudimentary, but efficient, walking. Recovery occurred well in advance of the expected time, and continued to improve up to allow the first patient operated on by connecting CNS with PNS to walk with sticks after having walked for some months with a walker. This connection functioned even if the axons activating the single muscles were from mother cells dispersed in different regions of the brain cortex. These cells fire together giving selective contraction of diverse muscles. Furthermore, function occurred although the upper motor neuron uses the neurotransmitter glutamate, whereas motor end plates use receptors for acetylcholine. These data are under further investigation to determine whether the upper motor neuron changes the transmitter, or if the motor end changes its receptors (as seems to be by the first results).

Electric Stimulation Therapy↗

PubMed2005

[Surgical repair of spinal cord injuries].

Spinal cord rupture is still incurable. Axons regenerating from the brain do not advance through the damaged cord towards peripheral motoneurons. The reasons for this "nonpermissiveness" are unclear. The author's research started in 1980 on rats and monkeys, with attempts to connect the lateral tract of the cord, upstream of the lesion, to the muscles, by means of autologous grafts. This operation was subsequently performed on fully informed volunteers with total cord rupture between T8 and T11. The first patient regained a rudimentary but effective gait. This connection of upper motoneurons with peripheral muscle nerves works even when the activating axons derive from cells dispersed among different regions of the brain cortex but that fire together, providing selective contraction of single muscles. Furthermore, this functioning occurs even though upper motor neurons use the neurotransmitter glutamate, whereas motor endplates normally have acetylcholine receptors. In fact, immunoblot analysis of ChAT VAChT, Vglu-1 GluR1 and GluR2 shows that motor endplate receptors switch from choline to glutamine.

Adult↗

PubMed2003

Making paraplegics walk again.

After attempting various types of research performed in different laboratories, this article describes the author's research that began in 1980 on rats, and continued since 1993 on monkeys. Also presented are results of the first clinical cases regarding operations performed either by rerouting the ulnar nerve to the lower limbs, or connecting the rostral stump of the severed cord with peripheral nerves of the hip to obtain rudimentary, but efficient, walking. Recovery occurred well in advance of the expected time, and continues to improve daily. This connection functioned even if the axons that activated the single muscles were from mother cells dispersed in different regions of the brain cortex, which fire together--such as in a teleassembly. Furthermore, function occurred although the upper motorneuron uses the neurotransmitter glutamate, whereas motor end plates use receptors for Acetilcholine. These data are under new investigation to determine whether the upper motorneuron changes the transmitter, or if the motor end plate changes its receptors.

Animals↗