- Home
- Knowledge Base
- References
Molecular neurosurgery with targeted toxins
Wiley RG, Lappi DA (2005) Molecular neurosurgery with targeted toxins. Humana Press, Totowa, New Jersey.
Summary: The idea behind the book was to provide a road map for the users of Molecular Neurosurgery to see how experienced scientists used these exceptional reagents in their work. Experiments with several targeted toxins are described, and readers can get an idea either specifically about a targeted toxin that they’re using, or about how a type of molecule is used and at what dosage, in a paradigm similar to theirs.
Related Products: 192-IgG-SAP (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), SSP-SAP (Cat. #IT-11), Dermorphin-SAP / MOR-SAP (Cat. #IT-12), IB4-SAP (Cat. #IT-10), CTB-SAP (Cat. #IT-14)
Featured Article: IB4-SAP prevents axotomy-induced sprouting of Aß fibers
Pearson M (2005) Featured Article: IB4-SAP prevents axotomy-induced sprouting of Aß fibers. Targeting Trends 6(1)
Related Products: IB4-SAP (Cat. #IT-10)
Read the featured article in Targeting Trends.
See Also:
The behavioral and neuroanatomical effects of IB(4)-saporin treatment in rat models of nociceptive and neuropathic pain.
Tarpley JW, Kohler MG, Martin WJ (2004) The behavioral and neuroanatomical effects of IB(4)-saporin treatment in rat models of nociceptive and neuropathic pain. Brain Res 1029(1):65-76. doi: 10.1016/j.brainres.2004.09.027
Summary: Using the fact that primary afferent neurons bind isolectin B4 (IB4), the authors injected 5 µg of IB4-SAP (Cat. #IT-10) into the sciatic nerve in the left thigh. After recovery, these animals were then treated with a L5 spinal nerve ligation. Lesioned animals displayed attenuated NGF-induced hyperalgesia, as well as differences in other pain-model markers. The data indicate that IB4-positive C-fibers play a discrete role in NGF-induced hyperalgesia, as well as in the development of neuropathic pain.
Related Products: IB4-SAP (Cat. #IT-10)
IB4-SAP reduces IB4 staining in the spinal cord and prevents axotomy induced sprouting of Aβ fibers
Pearson MS, Woods M, Whiteside GT, Garrison AE, Pomonis JD, Walker K (2004) IB4-SAP reduces IB4 staining in the spinal cord and prevents axotomy induced sprouting of Aβ fibers. Neuroscience 2004 Abstracts 858.6. Society for Neuroscience, San Diego, CA.
Summary: Peripheral nerve injury results in hyperalgesia and allodynia. It has been proposed that sprouting of myelinated touch responsive Aß-fibers into the innervation territory of pain sensitive C-fibers in the spinal cord contributes to these abnormal behaviors. The extent of sprouting has recently been challenged and it has been proposed that C-fibers rather than Aß-fibers are involved. We have investigated whether selectively ablating a population of small diameter nociceptors using isolectin B4 conjugated to saporin (IB4-SAP), reduces axotomy-induced sprouting. Male Sprague-Dawley rats received intraneural injections of either IB4-SAP or PBS (3 µl, 0.66 µg/µl) and two weeks later the sciatic nerve was axotomized at the mid-thigh level. Two weeks later, the sciatic nerve was injected with the retrograde tracer, cholera toxin-ß subunit (CTB) (2 µl, 2%) that selectively traces Aß-fibers. Three days post CTB the animals were perfused, the spinal cord harvested, sectioned and stained immunohistochemically for IB4 and CTB. IB4-SAP treatment resulted in a substantial reduction of IB4 staining in the spinal cord versus PBS injected controls. As previously described, axotomy resulted in considerable CTB immunostaining in laminae I, II and III compared to non-axotomized controls in which it was present only in laminae I and III. IB4-SAP treatment followed by axotomy resulted in a substantial reduction of CTB immunostaining in lamina II compared to PBS injected controls. These results suggest that intraneural IB4-SAP ablates a population of small diameter nociceptors and that axotomy induced CTB staining in lamina II is due to uptake of CTB by C-fibers.
Related Products: IB4-SAP (Cat. #IT-10)
ATS Poster of the Year Winner. Read the featured article in Targeting Trends.
Investigation of the functional role of non-peptidergic primary afferent sensory fibres in the transmission of pain related information
Bailey AL, Bennett G, Ribeiro-da-Silva A (2004) Investigation of the functional role of non-peptidergic primary afferent sensory fibres in the transmission of pain related information. Neuroscience 2004 Abstracts 484.1. Society for Neuroscience, San Diego, CA.
Summary: It is well established that small diameter, unmyelinated, primary afferent C-fibres can be divided into two neurochemically defined populations, one that contains neuropeptides such as Substance P (SP) and Calcitonin-gene related peptide (CGRP) and the other which binds Isolectin B4 (IB4) and is relatively peptide negative. A great deal of circumstantial evidence indicates that the non-peptidergic afferents play a functionally distinct role in pain transmission compared to peptidergic afferents. Indeed, the concept of two distinct subpopulations of C-fibres would indicate the occurrence of parallel processing in pain pathways. However, the functional role of non-peptidergic afferents in the transmission of pain-related information is still unclear. In an attempt to clarify their functional role, we decided to study the development of hyperalgesia and allodynia in adult male Sprague-Dawley rats with selective ablation of IB4-binding, non-peptidergic afferent input to the dorsal horn. To achieve this, we injected IB4 conjugated to Saporin (SAP) into the left sciatic nerve and examined both neurochemical and behavioural changes over a month’s time. Our data show that following injection of the toxin conjugate, IB4-labelling, P2X3-immunopositive fibre terminals disappear from a band in the superficial dorsal horn that expands over a two week period until it comprises most of the mediolateral extent of the dorsal horn. Behavioural data indicates that there are transient changes in acute pain thresholds to mechanical and thermal stimuli. Changes in pain thresholds in animals lacking non-peptidergic input into the spinal dorsal horn in an animal model of Complete Freund’s Adjuvant (CFA) induced inflammation will also be presented.
Related Products: IB4-SAP (Cat. #IT-10)
Featured Article: Effects of IB4-SAP on bladder overactivity
Yoshimura N (2004) Featured Article: Effects of IB4-SAP on bladder overactivity. Targeting Trends 5(4)
Related Products: IB4-SAP (Cat. #IT-10)
Read the featured article in Targeting Trends.
See Also:
Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation.
Nishiguchi J, Sasaki K, Seki S, Chancellor MB, Erickson KA, de Groat WC, Kumon H, Yoshimura N (2004) Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation. Eur J Neurosci 20(2):474-482. doi: 10.1111/j.1460-9568.2004.03508.x
Summary: It has been demonstrated that IB4-binding non-peptidergic C-fiber neuronal populations are present in afferent pathways to the bladder. The authors used intrathecal administration of 8 µl of 2.5 µM IB4-SAP (Cat. #IT-10) to investigate what roles these neurons play in bladder function. Treated animals displayed a reduction of IB4 afferent nerve terminal staining, as well as a suppression of bladder overactivity due to bladder irritation, without a change in normal bladder function.
Related Products: IB4-SAP (Cat. #IT-10)
Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death.
Sedel F, Béchade C, Vyas S, Triller A (2004) Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death. J Neurosci 24(9):2236-2246. doi: 10.1523/JNEUROSCI.4464-03.2004
Related Products: IB4-SAP (Cat. #IT-10)
Targeted toxins in pain.
Wiley RG, Lappi DA (2003) Targeted toxins in pain. Adv Drug Deliv Rev 55(8):1043-1054. doi: 10.1016/s0169-409x(03)00102-9
Summary: The authors discuss the use of ‘molecular neurosurgery’ in the study of nociception. Applications using targeted toxins, which include immunotoxins, protein-toxin conjugates, or peptide-toxin conjugates, are illustrated. The authors describe the use of these molecules as research tools, as well as their potential for therapeutics. A helpful table is included that lists neuronal surface markers and class of cells targeted for each targeted toxin. Reagents discussed: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-Saporin (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP (Cat. #IT-12), Orexin-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), and acetylated LDL-SAP (Cat. #IT-08).
Related Products: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-IgG-SAP (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Orexin-B-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), Acetylated LDL-SAP (Cat. #IT-08)
Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord.
Nakatsuka T, Tsuzuki K, Ling JX, Sonobe H, Gu JG (2003) Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord. J Neurophysiol 89(6):3243-3252. doi: 10.1152/jn.01172.2002
Summary: P2X receptors are important modulating neurons in the spinal cord. These authors used IB4-SAP (Cat. #IT-10) to target a neuronal subset, those neurons expressing P2X3 receptors. 2 µg of IB4-SAP were injected directly into the sciatic nerve on one side. Histological examination showed efficient removal of IB4 and P2X3-staining ipsilaterally in the dorsal horn outer laminae. Behavioral experiments showed intact modulation of glutamate release in the absence of P2X3-positive neurons, indicating involvement by other P2X neurons.
Related Products: IB4-SAP (Cat. #IT-10)